Leptin receptor and prolactin in pubertal disorders and chronic kidney disease.

BACKGROUND: Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12-month follow-up period. METHODS: A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients' clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients' thyroid profile, prolactin levels, luteinizing hormone, follicle-stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t-test and Fisher's exact tests. Logistic regression analysis was also performed. RESULTS: Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio [RR], 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD. CONCLUSIONS: Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.

The interplay between prolactin and cardiovascular disease.

Hyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.

Hyperprolactinemia as a prognostic factor for menstrual disorders in female adolescents with advanced chronic kidney disease.

BACKGROUND: In adolescents with chronic kidney disease (CKD), menstrual disorders (MD) are common, which can make the management of CKD difficult and can sometimes delay renal transplantation. This study aimed to identify the usefulness of hormonal measurements in adolescents with CKD and their relationships with MD during a 1-year follow-up. METHODS: A prospective cohort study was designed. Adolescents with CKD stages IV and V were included. Through clinical files and via interview, the ages at puberty onset, menarche and the date of last menstruation were identified. A 1-year follow-up was conducted over a menstrual cycle calendar. At the beginning of follow-up, routine hormonal profiles (thyroid profiles, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol) were assessed. We compared the hormonal profiles of the patients with and without MD (wMD vs. woMD). Comparisons between groups were made by Wilcoxon and Fisher's tests. Logistic regression analysis was used. RESULTS: Fifty-seven patients, including 30 patients classified as wMD, were analyzed. The median age was 15 years, and the median time of CKD evolution was 18 months. There were no differences in general and biochemical characteristics between patients wMD and woMD. In terms of hormonal measurements, the levels of thyroid-stimulating hormone (TSH) and prolactin were higher in the wMD patients. A prolactin level ≥ 36.8 ng/ml was a risk factor for presenting with MD (RR 34.4, p = 0.002). CONCLUSIONS: Hyperprolactinemia is correlated with MD in adolescents with CKD.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients.

METHODS: Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. RESULTS: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. CONCLUSION: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Löfgren Syndrome with Hypercalcemia and Neuroendocrinological Involvement: A Case Report.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease of unknown etiology that can affect virtually any organ. Löfgren syndrome, characterized by erythema nodosum, hilar lymphadenopathy, fever and polyarthritis, represents only 20-30% of the cases of sarcoidosis. Only 2- 10% of the cases feature hypercalcemia. CASE: The case of a 42-year-old Hispanic woman with a history of erythema nodosum and three weeks of nausea, emesis, constipation, asthenia, adynamia, polydipsia, and somnolence, concomitant with hypercalcemia, but normal parathyroid hormone (PTH) and 25-hydroxyvitamin D has been presented. The initial diagnostic approach was based upon the suspicion of multiple myeloma or bone metastases; however, further findings of bilateral hilar lymphadenopathy, elevated serum angiotensin-converting enzyme (ACE) and a right inguinal lymphadenomegaly suggested an alternate diagnosis. Biopsy of the latter supported sarcoidosis as the diagnosis. She was successfully treated in the hospital with zoledronic acid and as an outpatient with immunosuppressive therapy. Persistence of a previously undisclosed symptom of oligomenorrhea led to the detection of hyperprolactinemia secondary to hypophyseal infiltration, refractory to immunosuppressive therapy but with an adequate response to cabergoline. CONCLUSION: This case strays from Löfgren Syndrome's expected behavior, presenting a more progressive, multisystemic disease. This case report was written in adherence to the CARE guidelines of 2013 to include information in it.

Quiste de bolsa de Rathke e hiperprolactinemia, una causa infrecuente de amenorrea primaria / Rathke cleft cysts and hyperprolactinemia, an uncommon cause of primary amenorrhea

El quiste de la bolsa de Rathke es una lesión epitelial benigna de la región selar, formada a partir de remanentes embrionarios. La mayoría de los casos son asintomáticos, aunque pudiera presentarse con cefalea, disfunción hipofisaria y trastornos visuales, muy infrecuentemente como apoplejía hipofisaria. Se presenta el caso de una paciente que, habiendo presentado amenorrea primaria, se le realiza el diagnóstico de quiste de la bolsa de Rathke con hiperprolactinemia, logrando menarquia luego del tratamiento con cabergolina.

Rathke's cyst is a benign epithelial lesion of the sellar region, formed from embryonic remnants. Most cases are asymptomatic although it could present with headache, pituitary dysfunction and visual disorders, very infrequently as pituitary stroke. We present the case of a patient who, having presented primary amenorrhea, is diagnosed with Rathke's cyst with hyperprolactinemia, achieving menarche after treatment with cabergoline.

Tratamiento hormonal y sus complicaciones en el paciente con disforia de género / Hormonal treatment and complications in patients with gender dysphoria

RESUMEN Introducción: Las personas con disforia de género sienten incongruencia entre el sexo con el que nacen y aquel al que sienten pertenecer, por lo que necesitan adaptar su cuerpo a este último, y uno de los pilares en el logro de ese propósito es el empleo del tratamiento hormonal cruzado. Objetivo: Identificar los esquemas terapéuticos más empleados en la automedicación y en el manejo especializado, y sus complicaciones en pacientes con disforia de género. Métodos: Se revisaron 78 historias, de las cuales 76 correspondían a transexuales hombre-mujer, atendidos en el periodo 2012-2017 en la Consulta Nacional de Atención Integral a Personas Transgénero. Se recuperó información relacionada con los esquemas terapéuticos utilizados, tanto durante la automedicación como durante el manejo por el endocrinólogo, y las complicaciones. Para el análisis de los datos se obtuvieron distribuciones de frecuencia de las variables cualitativas, media y desviación estándar de las cuantitativas. Resultados: La frecuencia de pacientes que se autoadministraron hormonas antes de comenzar la atención especializada fue de 82,9 por ciento. El medicamento más utilizado en la automedicación fue la cipresta (acetato de ciproterona 2 mg/etinilestradiol 50 µg) en el 90,5 por ciento de los casos. De los tratamientos indicados por el endocrinólogo al inicio de la atención; al 50,0 por ciento se les administró cipresta más androcur (acetato de ciproterona 50 mg) de 1 a 2 tabletas de cada uno, mientras que al 39,5 por ciento estrógenos conjugados asociado a androcur, igualmente de 1 a 2 tabletas de cada uno de estos medicamentos. En cuanto a la frecuencia de complicaciones como consecuencia del tratamiento hormonal, el 40,7 por ciento de los casos tuvo en algún momento niveles elevados de prolactina, al 26,3 por ciento los niveles de triglicéridos se le elevaron luego de iniciada la terapia. Conclusiones: La mayoría de los pacientes acuden por primera vez automedicados. Los medicamentos más utilizados son la cipresta y el androcur. La complicación más frecuente como consecuencia del tratamiento es la hiperprolactinemia(AU)

ABSTRACT Introduction: Persons with gender dysphoria feel incongruity between the sex they are born with and the one they feel they belong to, therefore they need to adapt their body to the latter, and one of the pillars in achieving that purpose is the use of cross hormonal treatment. Objective: To identify the therapeutic schemes most used in self-medication and specialized management, and their complications in patients with gender dysphoria. Methods: Seventy eight medical records were reviewed. Seventy six of them corresponded to male-female transsexuals, assisted in the 2012-2017 period at the National Consultation of Comprehensive Care to Transgender Persons. The study team recovered information related to the therapeutic schemes used, both during self-medication and during the endocrinological management, as well as complications. Frequency distributions of the qualitative variables, mean and standard deviation of the quantitative variables were obtained for data analysis. Results: The frequency of patients who self-administered hormones before beginning specialized care was 82.9 percent. The most commonly medication used in self-medication was cypress (cyproterone acetate 2 mg / ethinylestradiol 50 µg) in 90.5 percent of cases. Out of the treatments indicated by the endocrinologist at the beginning of the care; 50.0 percent were given cypress plus androcur (50 mg cyproterone acetate) of 1 to 2 tablets each, while 39.5 percent conjugated estrogens associated with androcur, also 1 to 2 tablets of each of these medications. Regarding the frequency of complications as a result of hormonal treatment, 40.7 percent of the cases had elevated prolactin levels at some time, and triglyceride levels increased to 26.3 percent after the start of therapy. Conclusions: Most patients who come for the first time, are self-medicated. The most used medications are cipresta and androcur. The most frequent complication is hyperprolactinemia as a consequence of treatment(AU)

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.

[Frequency of increased thyrotropin in women with hyperprolactinemia]. / Frecuencia de tirotropina elevada en mujeres con hiperprolactinemia.

BACKGROUND: Hypothyroidism has been associated to hyperprolactinemia. The aim was to establish the frequency of high thyrotropin (TSH) levels in women with hyperprolactinemia. METHODS: Retrospective, observational, open, and non-controlled study, which included all the non-pregnant women whose prolactin (PRL) and TSH levels were measured between January 1 and December 31, 2014. RESULTS: 437 women were studied. The most frequent diagnoses that motivated PRL measurement were: infertility (31.7%), polycystic ovary syndrome (18.7%), and amenorrhea (7.8%). In the whole group TSH levels were 2.5 ± 2.7 µUl/mL and those of PRL 16.5 ± 13.2 ng/dL. From the total of women, those with normal PRL levels, 1.4% had low TSH levels, 76.6% normal and 7.5% high, while in those with high PRL levels 0.7% had low TSH levels 12.6% normal and 1.1% high. Of those 374 patients with normal PRL, 6 (1.6%) had low TSH levels, 335 (89.6%) normal TSH levels, and 33 (8.8%) high TSH levels. Of those 63 patients with high PRL, 3 (4.8%) had low TSH levels, 55 (87.3%) normal TSH and 5 (7.9%) high TSH levels. CONCLUSION: In this study it was not possible to document that the proportion of patients with high TSH was greater in those with hyperprolactinemia.

Introducción: el hipotiroidismo se suele asociar con hiperprolactinemia (HPRL). Se buscó determinar la frecuencia de tirotropina (TSH) elevada en mujeres con HPRL. Métodos: estudio retrospectivo, observacional, abierto y no controlado que incluyó a todas las mujeres no embarazadas en quienes se detectó la prolactina (PRL) y la TSH del 1 de enero al 31 de diciembre de 2014. Resultados: se estudiaron 437 mujeres. Los diagnósticos que motivaron la solicitud de PRL fueron: infertilidad (31.7%), síndrome de ovarios poliquísticos (18.7%) y amenorrea (7.8%). En el grupo completo las concentraciones de TSH fueron 2.5 ± 2.7 µUl/mL y las de PRL 16.5 ± 13.2 ng/dL. Del total de pacientes, aquellas con PRL normal, 1.4% tuvo TSH baja, 76.6% TSH normal y 7.5% elevada, mientras que de aquellas con PRL elevada 0.7% tuvo TSH baja, 12.6% normal y 1.1% elevada. De las 374 pacientes que tenían PRL normal, 6 (1.6%) presentaron TSH disminuida, 335 (89.6%) TSH normal y 33 (8.8%) TSH elevada. De las 63 pacientes con PRL elevada, 3 (4.8%) presentaron TSH disminuida, 55 (87.3%) TSH normal y 5 (7.9%) TSH aumentada. Conclusión: no se logró documentar que la proporción de pa-cientes con TSH elevada fuera mayor en aquellas con HPRL.

Interactions between prolactin and kisspeptin to control reproduction.

Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin's functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin's actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.

Interactions between prolactin and kisspeptin to control reproduction

ABSTRACT Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin’s functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin’s actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.

Diagnosis and Management of Breast Milk Oversupply.

Managing breastfeeding problems is an essential part of newborn care. While much is written on breast milk undersupply, little is written on oversupply, sometimes known as hyperlactation or hypergalactia. Infants of mothers with oversupply may have increased or decreased weight gain. Some may have large, frothy stools. They may develop a disordered latch. Mothers may report overly full, leaking breasts. Thyroid function should be assessed. Treatment is mostly anecdotal and includes methods to maintain breast fullness, such as block feedings. Pseudoephedrine and oral contraceptive pills may decrease the supply. Dopamine agonists such as carbergoline can be used as a last resort.

Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats.

UNLABELLED: Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. AIMS: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. MATERIAL AND METHODS: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. RESULTS: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. CONCLUSION: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies.

Prolactinomas.

Identifying the correct cause of hyperprolactinemia is crucial for treatment. Prolactinoma is the most common pathologic cause of hyperprolactinemia. Dopamine agonists are efficacious in about 80% to 90% of patients with prolactinoma, leading to reduction of serum prolactin levels and tumor dimensions. Neurosurgery, mainly by the transsphenoidal route, is indicated in cases of intolerant and resistant dopamine agonists. Radiotherapy is rarely used because of its side effects and low efficacy. The alkylating agent temozolomide showed efficacy for treatment of aggressive and resistant prolactinomas. Other approaches, such as thyrosine kinase inhibitors, are currently being tested and could be an additional tool for these troublesome tumors.

Hiperprolactinemia y disfunción sexual en el varón / Hyperprolactinemia and sexual dysfunction among males

Hyperprolactinemic males usually have a hypoactive libido and less commonly, erectile dysfunction and disturbances of orgasm and ejaculation. Hyperprolactinemia alters the balance between neurotransmitters, neuropeptides and hormones involved in libido and erection, affecting dopaminergic tone. An imbalance between dopamine, that stimulates sexual function and serotonin that inhibits it, is generated. In the central nervous system, hyperprolactinemia inhibits centers controlling sexual desire and erection. At the neuroendocrine level, it decreases GnRH, LH and testosterone pulses, resulting in a hypogonadotrophic hypogonadism. Erection is also inhibited peripheral actions of low testosterone and high prolactin levels. There is a disturbance of penile smooth muscle relaxation and of the parasympathetic sacrum-penis reflex arch. In experimental animals, acute hyperprolactinemia hampers the central erection mechanism whereas in chronic conditions, peripheral disturbances also occur. Even correcting low testosterone levels, the adverse effects of hyperprolactinemia on sexual function persist. The use of dopaminergic agonists may achieve normal prolactin and testosterone levels resulting in normal sexual function. Chronic hyperprolactinemia results in progressive deterioration of sexual function and a higher hypothalamic damage that does not respond to clomiphene. In this situation and in the presence of sellar tumors that destroy gonadotrophic cells, there is indication of androgenic replacement maintaining the use of dopaminergic agonists...

Giant macroprolactinoma and pregnancy.

Prolactinomas are a common cause of gonadal dysfunction and infertility. We present the case of a 38-year-old woman with history of amenorrhea and infertility. At seven weeks of pregnancy she presented neuro-ophthalmologic complaints of headaches, diplopia, and right ptosis. The work-up study revealed an invasive pituitary macroadenoma with a maximum diameter of 9 cm and serum prolactin of 25,800 ng/mL (3-20). At 12 weeks, she was referred to the Endocrinology Department of the Coimbra University Hospital and started therapy with bromocriptine, initially 5 mg/day and then at crescent doses. Hyperprolactinemia was rapidly and drastically reduced to 254 ng/mL three weeks after taking bromocriptine 15 mg/day. Tumoral volume was reduced and there was improvement of III pair paresis. At 38 weeks, a male healthy baby was born. This is a relevant clinical case that illustrates the efficacy and safety of bromocriptine therapy during pregnancy, even in severe cases like this one.

Hyperprolactinemia impairs object recognition without altering spatial learning in male rats.

Prolactin (PRL) exerts protective effects on the hippocampus against chronic stress exposure, or kainic acid insults. Further, PRL null mice were recently shown to exhibit learning and memory deficits. These findings suggest the hippocampus as a PRL target. To test this hypothesis, we analyzed the hippocampal formation function in dependence of serum PRL concentrations. Male Sprague-Dawley rats were either transplanted with 2 pituitary homografts (HPRL) or had a sham operation (SHAM). Other groups were given vehicle (VEH) or daily injections of bromocriptine (BRC, 4mg/kg) to reduce PRL levels. The animals were sequentially subjected to the Morris water maze (MWM), the object recognition test and the elevated plus maze. PRL concentrations were measured with ELISAs. Learning curves from the MWM showed a progressive reduction in distance over time but no significant differences were found between SHAM and HPRL, or between BRC and VEH groups. Also, memory retrieval was not affected in the probe trial between each pair of groups. However, in the object recognition test the HPRL group failed to discriminate between novel and familiar objects, and the discrimination index was significantly reduced from that of the VEH group. BRC rats exhibited a reduced exploration of both objects compared to VEH, but had a discrimination index similar to VEH. No significant differences were observed in the EPM. In conclusion, high PRL levels impair object recognition but do not alter spatial learning. These results show for the first time that PRL impairs object recognition, and thus modulates non-spatial cognitive tasks.

Short-term pharmacological suppression of the hyperprolactinemia of infertile hCG-overproducing female mice persistently restores their fertility.

Female infertility is often associated with deregulation of hormonal networks, and hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis affecting the reproductive functions. We have shown previously that transgenic female mice overexpressing human chorionic gonadotropin ß-subunit (hCGß+ mice), and producing elevated levels of bioactive LH/hCG, exhibit increased production of testosterone and progesterone, are overweight and infertile, and develop hyperprolactinemia associated with pituitary lactotrope adenomas in adult age. In the present study, we analyzed the influence of the hyperprolactinemia of hCGß+ females on their reproductive phenotype by treating them with the dopamine agonists, bromocriptine and cabergoline. Long-term bromocriptine treatment of adult mice was effective in the control of obesity, pituitary growth, and disturbances in the hormone profile, demonstrating that hyperprolactinemia was the main cause of the hCGß+ female phenotype. Interestingly, short-term treatment (1 wk) with cabergoline applied on 5-wk-old mice corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, prevented pituitary overgrowth, normalized gonadal function, and recovered fertility of adult hCGß+ females after hormone-induced and natural ovulation. The same cabergoline treatment in the short term applied on 3-month-old hCGß+ females failed to recover their reproductive function. Hence, we demonstrated that the short-term cabergoline treatment applied at a critical early stage of the phenotype progression effectively prevented the hyperprolactinemia-associated reproductive dysfunction of hCG-overproducing females.