- Dopamine agonists for preventing future miscarriage in women with idiopathic hyperprolactinemia and recurrent miscarriage history. [REVIEW, JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2016 Jul 25.:CD008883.
Hyperprolactinemia is the presence of abnormally high circulating levels of prolactin. Idopathic hyperprolactinemia is the term used when no cause of prolactin hypersecretion can be identified and it is causally related to the development of miscarriage in pregnant women, especially women who have a history of recurrent miscarriage. A possible mechanism is that high levels of prolactin affect the function of the ovaries, resulting in a luteal phase defect and miscarriage. A dopamine agonist is a compound with high efficacy in lowering prolactin levels and restoring gonadal function.To assess the effectiveness and safety of different types of dopamine agonists in preventing future miscarriage given to women with idiopathic hyperprolactinemia and a history of recurrent miscarriage.We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2016) and reference lists of retrieved studies.Randomized controlled trials (RCTs) in all languages examining the effect of dopamine agonists on preventing future miscarriage. Women who had idiopathic hyperprolactinemia with a history of recurrent miscarriages were eligible for inclusion in this review. Comparisons planned included: dopamine agonists alone versus placebo/no treatment; and dopamine agonists combined with other therapy versus other therapy alone.Two review authors independently assessed a single trial for inclusion, evaluated trial quality and extracted data. Data were checked for accuracy.One study (recruiting 48 women with idiopathic hyperprolactinemia) met our inclusion criteria; 46 women (42 pregnancies - 4/46 women did not conceive during the study period) were included in the analysis. The study compared the use of a dopamine agonist (bromocriptine, 2.5 mg to 5.0 mg/day until the end of the ninth week of gestation) versus a no-treatment control. The study was judged as being at a high risk of bias. It was not possible to carry out meta-analysis due to insufficient data.The study reported both of this review's primary outcomes of miscarriage and live birth. Results from this single study suggest that, compared to no treatment, oral bromocriptine was effective in preventing future miscarriage (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.09 to 0.87, 46 participants (low-quality evidence)) in women with idiopathic hyperprolactinemia. There was no clear difference with regard to the other primary outcome of live births (RR 1.50, 95% CI 0.93 to 2.42, 46 participants (very low-quality evidence)).There was no difference with regard to this review's secondary outcome of conception (RR 0.92, 95% CI 0.77 to 1.09, 46 participants (very low-quality evidence)) between the group of women who received dopamine (21 out of 24 women conceived) and women in the no-treatment group (21 out of 22 women conceived). The included study only reported the serum prolactin levels in pregnant women and therefore the data could not be analyzed in this review. No other secondary outcomes relevant to this review were reported; adverse effects for women (nausea, vomiting, headache, vertigo, fatigue, hypotension, arrhythmia, and psychotic symptoms) and infants (birth defects, low birthweight, and developmental disabilities) were not reported.We downgraded the quality of the evidence for risk of bias in the one trial contributing outcome data (no description of allocation concealment, lack of blinding and possible reporting bias) and for imprecision (all effect estimates were based on small sample size, miscarriage was based on few events, and the 95% CIs of live birth and conception cross the line of no effect).Currently, there is insufficient evidence (from a single randomized trial with a small sample size, and judged to be at high risk of bias) to evaluate the effectiveness of dopamine agonists for preventing future miscarriage in women with idiopathic hyperprolactinemia and a history of recurrent miscarriage. We assessed outcomes using GRADE methodology. Miscarriage was assessed as low quality due to risk of bias concerns in the one trial contributing data (no description of allocation concealment, lack of blinding and possible reporting bias) and to imprecision (effect estimates were based on small sample size and few events). Live births and conception were assessed as of very low quality due to the same risk of bias concerns in study design and to imprecision (with a wide 95% CI consistent with either benefit or harm), and a small sample size. There were no data relating to adverse effects of the intervention for either the mother or her baby.Futher high-quality research in this area is warranted. There is a need for well-designed, larger RCTs to confirm and extend the findings of the trial reviewed here. Many questions remain unanswered. Some important considerations for future research include, the need for well-designed RCTs with large sample sizes, and for those studies to consider important outcomes (including adverse effects for both the mother and her baby). Future studies should examine the effectiveness and safety of various dopamine agonists including bromocriptine, cabergoline and quinagolide.
- Testosterone undecanoate improves lipid profile in patients with type 1 diabetes and hypogonadotrophic hypogonadism. [JOURNAL ARTICLE]
- Endocr J 2016 Jul 22.
Testosterone deficiency (Td) has been associated with the metabolic syndrome. Few studies have evaluated this condition in type 1 diabetes (T1D). The primary aim of this study was to evaluate the effectiveness of testosterone undecanoate (TU) on insulin sensitivity, glycemic control, anthropometric parameters, blood pressure and lipid profile in patients with Td and T1D. We performed a randomized placebo-controlled multicenter study.a) age ≥ 18 years; b) autoimmune diabetes; c) Td (total testosterone <10 nmol/L or calculated free testosterone <225 pmol/L and low/normal LH; d) ability to sign informed consent; e) comply with the study protocol.a) pituitary tumor, empty sella, hyperprolactinemia, panhypopituitarism or secondary hypogonadism; b) contraindications for treatment with testosterone undecanoate (TU); c) patients who did not agree to sign their informed consent. Six patients were randomly assigned to testosterone undecanoate (TU) treatment and 7 to placebo with the following dosing schedule: baseline, 6 weeks and 16 weeks. Blood test, anthropometric parameters, blood pressure and insulin sensitivity were determined at baseline, 6, 16 and 22 weeks. No differences were observed regarding insulin sensitivity, HbA1c or basal glucose, anthropometric parameters or blood pressure. At 22 weeks, the decrease in total cholesterol was 37.4 ± 27.5 mg/dL in the TU group compared with an increase of 13.2 ± 17.8 mg/dL in the placebo group (P<0.005), and LDL cholesterol concentration decreased 30.2 ± 22.1 mg/dL, compared with an increase of 10.5 ± 13.4 mg/dL in the placebo group (P=0.004). We conclude that treatment with TU in patients with T1D and Td improves lipid profile, with no effects on metabolic control or anthropometric parameters.
- Biopsy proven pituitary sarcoidosis presenting as a possible adenoma. [JOURNAL ARTICLE]
- J Clin Neurosci 2016 Jul 21.
Sarcoidosis is a well-recognized systemic granulomatous process which involves the central nervous system in 5-15% of patients. One of the more frequent sites of central nervous system involvement is the pituitary and hypothalamic region. Involvement of the sellar region by sarcoidosis is overall an infrequent occurrence, comprising less than 1% of all intrasellar lesions. Patients typically present with an infiltrative lesion on imaging studies and clinically with symptoms related to diabetes insipidus or hyperprolactinemia. This report describes a 38-year-old woman who initially presented with a variety of symptoms including headaches, light sensitivity, nausea and vomiting, acute visual changes, cold intolerance, amenorrhea, decreased libido, fatigue and galactorrhea. She had an elevated serum prolactin level and evidence of oligoclonal bands in the cerebrospinal fluid. Imaging studies discovered a 1.8cm mass involving the pituitary gland and compressing the optic chiasm. The lesion was excised and microscopically was marked by a chronic inflammatory cell infiltrate and scattered nonnecrotizing granulomas. Stains and microbiologic cultures failed to demonstrate microorganisms. There was no evidence of other organ involvement on postoperative imaging. She was treated with prednisone with improvement of symptoms and subsequently required methotrexate to treat left eye pain and blurred vision, 29months after her surgery. Achieving treatment control in patients with pituitary and hypothalamic improvement in sarcoidosis still remains a challenge.
- Hyperprolactinemia Secondary to Pituitary Microadenoma versus Haloperidol-A Diagnostic Enigma: A Case Report and Brief Review. [JOURNAL ARTICLE]
- Curr Drug Saf 2016 Jul 19.
Hyperprolactinemia can be caused by medications, primarily antipsychotics, or by anterior pituitary tumors. The consequences of hyperprolactinemia including gynecomastia, galactorrhea, and sexual dysfunction are very disturbing for males and females. It is sometimes difficult to differentiate the etiology of hyperprolactinemia from a clinical perspective.Identification of the etiology of hyperprolactinemia requires a careful review of the causes and appropriate work-up.A 55-year-old African American male with extensive psychiatric history and non-adherence to treatment was admitted from nursing home for aggression and psychotic symptoms. The patient was noted to have mild bilateral breast enlargement about ten days after hospitalization. Prolactin level done on August 26, 2014 was 93.8 ng/mL, and on September 5, 2014 was 112 ng/mL. The patient's medications included haloperidol decanoate 150 mg q28d, haloperidol 10 mg po bid and benztropine 0.5 mg po bid. He did not have any other clinical signs or symptoms of hyperprolactinemia. He was also seen by an endocrinologist. MRI of the pituitary gland done on September 3, 2014, showed a 2.4 mm pituitary microadenoma. Bromocriptine was started at 1.25 mg qhs and titrated to 2.5 mg bid.Prolactin level dropped from 112 ng/mL on September 5, 2014 to 99 ng/mL on September 9, 2014, 61.2 ng/mLon September 23, 2014 and 3.0 ng/mL on February 9, 2015.Diagnosis and etiology of hyperprolactinemia were complicated by the minimal nature of clinical symptoms, the type of antipsychotic agent and the prolactin level. The MRI facilitated the diagnosis of pituitary microadenoma and further treatment option with bromocriptine. MRI of the pituitary is indicated for patients with hyperprolactinemia where the etiology is not clearly due to medication.
- Comparing the Effectiveness and Safety of the Addition of and Switching to Aripiprazole for Resolving Antipsychotic-Induced Hyperprolactinemia: A Multicenter, Open-Label, Prospective Study. [JOURNAL ARTICLE]
- Clin Neuropharmacol 2016 Jul 19.
Hyperprolactinemia is an important but often overlooked adverse effect of antipsychotics. Several studies have shown that switching to or adding aripiprazole normalizes antipsychotic-induced hyperprolactinemia. However, no study has directly compared the effectiveness and safety of the 2 strategies.A total of 52 patients with antipsychotic-induced hyperprolactinemia were recruited. Aripiprazole was administered to patients with mild hyperprolactinemia (serum prolactin level < 50 ng/mL). Patients with severe hyperprolactinemia (serum prolactin level > 50 ng/mL) were randomized to an aripiprazole-addition group (adding aripiprazole to previous antipsychotics) or a switching group (switching previous antipsychotics to aripiprazole). Serum prolactin level, menstrual disturbances, sexual dysfunction, psychopathologies, and quality of life were measured at weeks 0, 1, 2, 4, 6, and 8.Both the addition and switching groups showed significantly reduced serum prolactin level and menstrual disturbances and improved sexual dysfunction. In patients with severe hyperprolactinemia, the numbers of patients with hyperprolactinemia and menstrual disturbance in the switching group were significantly lower than those in the addition group at week 8.Both the addition and switching strategies were effective in resolving antipsychotic-induced hyperprolactinemia and hyperprolactinemia-related adverse events, including menstrual disturbances and sexual dysfunction. In addition, these findings suggest that switching to aripiprazole may be more effective than addition of aripiprazole for normalizing hyperprolactinemia and improving hyperprolactinemia-related adverse events in patients with schizophrenia.
- The epidemiology of hyperprolactinaemia over 20 years in the Tayside region of Scotland: The Prolactin Epidemiology, Audit, and Research Study (PROLEARS). [JOURNAL ARTICLE]
- Clin Endocrinol (Oxf) 2016 Jul 19.
To estimate the prevalence and incidence of hyperprolactinaemia. Hyperprolactinaemia is a common problem in endocrine practice, but its epidemiology has not been accurately established.A population-based retrospective follow up study in Tayside, Scotland (population 400,000) from 1993 to 2013.Record-linkage technology (biochemistry, prescribing, hospital admissions, radiology, mortality and maternity data) was used to identify all patients with a serum prolactin measurement. From these, cases were defined as those with a prolactin greater than 1000mU/L (47.2ng/ml) or at least three prescriptions for a dopamine agonist.Number of prevalent and incident cases of hyperprolactinaemia per calendar year by age, sex and cause of hyperprolactinaemia.A total of 32,289 patients had a serum prolactin assay undertaken, of which 1,301 had hyperprolactinaemia not related to pregnancy: 25.6% patients were pituitary-disorder 45.9% drug-induced, 7.5% related to macroprolactin, and 6.1% related to hypothyroidism, leaving 15.0% idiopathic. Over the 20 years there was a fourfold increase in the number of prolactin assays performed and prevalence of hyperprolactinaemia was initially 0.02%, but rose to 0.23% by 2013. Overall incidence was 13.8 cases per 100,000 person-years (20.6 in 2008-13) and was 3.5 times higher in women than in men. The highest rates were found in women aged 25-44 years. Drug-induced causes tripled during the 20 years.Rising prevalence of hyperprolactinaemia is probably due to increased ascertainment and increased incidence of psychoactive drug-related causes. Rates are higher in women than in men but only before the age of 65 years. This article is protected by copyright. All rights reserved.
- How Hyperprolactinemia Affects Sexual Function in Patients Under Antipsychotic Treatment. [JOURNAL ARTICLE]
- J Clin Psychopharmacol 2016 Jul 18.
We aimed to study the relationship between hyperprolactinemia (HPRL) and sexual dysfunction (SED) in a sample of patients being prescribed a dose-stable antipsychotic medication, and to evaluate sex differences in the prevalence of HPRL and SED and their relationship.A cross-sectional study was carried out including patients between 18 and 55 years of age with a psychotic spectrum diagnosis who were attending community mental health services or hospitalized in medium and long stay units. Positive and Negative Syndrome scale, Calgary depression scale for schizophrenia, Personal and Social Performance scale, and Changes in Sexual Functioning questionnaire-short form were administered. Not later than 3 months, a determination of prolactin, follicle-stimulating hormone, luteinizing hormone, estrogen (only in women) and testosterone was performed.A final sample of 101 patients (30 women and 71 men) was recruited. Seventy-two patients (71.3%) showed HPRL. Sexual dysfunction was significantly higher in HPRL patients than in non-HPRL patients (79.17% vs 51.72%) (P = 0.006), and mean prolactin values were significantly higher in case of SED (P = 0.020). No sex differences were found in prevalence of HPRL or SED. Low Personal and Social Performance scale scores and HPRL were factors independently associated with SED, whereas alcohol use was an independent protector factor.In our study, SED was significantly related to HPRL without showing sex differences. Prevalence of HPRL and SED observed was higher than that in previous studies, which should be taken into consideration because these have been associated with higher morbimortality, and noncompliance and relapse, respectively.
- Reproductive Health Assessment of Female Elephants in North American Zoos and Association of Husbandry Practices with Reproductive Dysfunction in African Elephants (Loxodonta africana). [Journal Article]
- PLoS One 2016; 11(7):e0145673.
As part of a multi-institutional study of zoo elephant welfare, we evaluated female elephants managed by zoos accredited by the Association of Zoos and Aquariums and applied epidemiological methods to determine what factors in the zoo environment are associated with reproductive problems, including ovarian acyclicity and hyperprolactinemia. Bi-weekly blood samples were collected from 95 African (Loxodonta africana) and 75 Asian (Elephas maximus) (8-55 years of age) elephants over a 12-month period for analysis of serum progestogens and prolactin. Females were categorized as normal cycling (regular 13- to 17-week cycles), irregular cycling (cycles longer or shorter than normal) or acyclic (baseline progestogens, <0.1 ng/ml throughout), and having Low/Normal (<14 or 18 ng/ml) or High (≥14 or 18 ng/ml) prolactin for Asian and African elephants, respectively. Rates of normal cycling, acyclicity and irregular cycling were 73.2, 22.5 and 4.2% for Asian, and 48.4, 37.9 and 13.7% for African elephants, respectively, all of which differed between species (P < 0.05). For African elephants, univariate assessment found that social isolation decreased and higher enrichment diversity increased the chance a female would cycle normally. The strongest multi-variable models included Age (positive) and Enrichment Diversity (negative) as important factors of acyclicity among African elephants. The Asian elephant data set was not robust enough to support multi-variable analyses of cyclicity status. Additionally, only 3% of Asian elephants were found to be hyperprolactinemic as compared to 28% of Africans, so predictive analyses of prolactin status were conducted on African elephants only. The strongest multi-variable model included Age (positive), Enrichment Diversity (negative), Alternate Feeding Methods (negative) and Social Group Contact (positive) as predictors of hyperprolactinemia. In summary, the incidence of ovarian cycle problems and hyperprolactinemia predominantly affects African elephants, and increases in social stability and feeding and enrichment diversity may have positive influences on hormone status.
- Serotonin and Antidepressant SSRIs Inhibit Rat Neuroendocrine Dopamine Neurons: Parallel Actions in the Lactotrophic Axis. [Journal Article]
- J Neurosci 2016 Jul 13; 36(28):7392-406.
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression, but sexual side effects often compromise compliance. These reproductive dysfunctions are likely mediated by elevations of the hormone prolactin. Yet, how serotonin (5-HT) and SSRIs cause changes in prolactin secretion is not known. Here, using in vitro whole-cell patch-clamp recordings, we show that 5-HT hyperpolarizes and abolishes phasic discharge in rat neuroendocrine tuberoinfundibular dopamine (TIDA) neurons, the main inhibitor of prolactin secretion. This process is underpinned by 5-HT1A receptor-mediated activation of G-protein-coupled inwardly rectifying K(+)-like currents. We further demonstrate that the SSRIs, fluoxetine and sertraline, directly suppress TIDA neuron activity through parallel effects, independent of 5-HT transmission. This inhibition involves decreased intrinsic excitability and a slowing of TIDA network rhythms. These findings indicate that SSRIs may inhibit neuroendocrine dopamine release through both 5-HT-dependent and -independent actions, providing a mechanistic explanation for, and potential molecular targets for the amelioration of, the hyperprolactinemia and sexual dysfunction associated with these drugs.Depression affects approximately one-tenth of the population and is commonly treated with selective serotonin reuptake inhibitors (SSRIs; e.g., Prozac). Yet, many patients withdraw from SSRI therapy due to sexual side effects (e.g., infertility, menstrual disturbances, and impotence). Although it is generally accepted that sexual side effects are due to the ability of these drugs to elevate blood levels of the hormone prolactin, the mechanism for this hormonal imbalance is not known. Here, we show that SSRIs can inhibit hypothalamic dopamine neurons that normally suppress the secretion of prolactin. Intriguingly this inhibition can be explained both by increased serotonin activity and also by parallel serotonin-independent actions.
- [Chronic kidney disease associated with Poems syndrome: Report of one case]. [English Abstract, Journal Article]
- Rev Med Chil 2016 Apr; 144(4):516-20.
POEMS syndrome is characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes. We report a woman with the syndrome, who had peripheral polyneuropathy, osteosclerotic myeloma, monoclonal IgA elevation, hypothyroidism, hypogonadotrophic hypogonadism, hyperprolactinemia, adrenal insufficiency, hepatosplenomegaly, lymphadenopathy, thyroid and parotid enlargement, Castleman’s disease, papilledema, stiff and hyperpigmented skin, white nails, clubbing, ascites and chronic diarrhea. She had also a nephropathy characterized by microscopic hematuria, proteinuria, renal insufficiency and a unilateral kidney retraction. She was treated with melphalan and prednisone, achieving remission of the disease and nephropathy. She survived twelve years and died due to a myocardial infarction 20 years after POEMS diagnosis.