Prolactin as a neuroendocrine clue in sexual function of women across the reproductive life cycle: an expert point of view.

Prolactin is a proteic hormone best known for its role in enabling the production of milk by female mammals. Secreted by the pituitary gland in response to the stimuli of eating, estrogen treatment, mating, ovulation and nursing, prolactin is involved in over 300 separate processes in a range of vertebrates, including humans. The hormone is released in a pulsatile manner and plays an essential role in metabolism, as well as in the regulation of the immune system and pancreatic development. Nevertheless, prolactin exerts other relevant roles, as it acts at the central nervous system level to modulate behavior, arousal and sexuality. In this experts' opinion, we aim to give insights into the main activities of prolactin to advance the ability of medical doctors and specialists in obstetrics and gynecology to provide more emphasis in their clinical practices to the link between prolactin and sexuality.

Monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia.

The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines.

Clinical profile and early therapeutic response to cabergoline of patients with hyperprolactinemia in a Cameroonian population.

Hyperprolactinemia is responsible for 20 to 25% of consultations of secondary amenorrhea and 17% for female infertility. Dopamine agonists are the gold standard treatment of hyperprolactinemia. Although they are associated with various adverse effects, cabergoline is generally preferred due to better compliance, limited side effects and good therapeutic response. However, bromocriptine is widely and satisfactorily used in a context of limited availability of cabergoline. We sought to describe clinical manifestations of hyperprolactinemia and response to cabergoline in a sub Saharan Africa (SSA) setting. We describe the profile of all patients with a diagnosis of hyperprolactinaemia from 1st July 2012 to 15th May 2014 at the Endocrinology Department of Yaoundé Central Hospital. Patients with physiological hyperprolactinemia were not considered. All patients were routinely started on cabergoline at 0.5mg/week or at 1mg/week in case of macroprolactinoma or desire to become pregnant. The duration of follow up was 8-16 months. After three months of treatment, 8 of 10 patients with amenorrhea had menses and serum prolactin levels decreased significantly at month 2-3 (p = 0.025). In conclusion, our study suggests that cabergoline yields an excellent therapeutic response in a short period of time and may thus be cost saving in sub Saharan context despite its unit price.

[Research progress of kisspeptin in female reproductive endocrine and assisted reproductive techniques].

In recent years, it has been found that kisspeptin plays some key roles in the physiological processes of the brain, such as gender differentiation, positive and negative feedback of sex hormones, onset of puberty, and transduction of energy signals in the body, which suggests that kisspeptin may be a key molecule for the maturation and regulation of female reproductive function. In addition to the systemic roles of the kisspeptin, its local roles in reproductive organs are constantly being discovered. With the discovery that kisspeptin is involved in the pathological process of reproductive endocrine diseases such as isolated hypogonadotropic hypogonadism (IHH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF) and pathological hyperprolactinemia, exogenous application of kisspeptin to solve reproductive problems has become a new hot topic. The review focuses on the research progress of kisspeptin in the female reproductive system, especially on its application in assisted reproduction.

Prolactin is Not Associated with Disability and Clinical Forms in Patients with Multiple Sclerosis.

An association between prolactinemia with disability, clinical forms, and sex of patients with multiple sclerosis (MS) remains unclear. The aim of this study was to evaluate the association of prolactin with clinical forms and accumulating disability over time in patients with MS. A longitudinal study was carried out with 101 patients with relapsing-remitting MS (RRMS) and 19 with progressive forms of MS (ProgMS). The disability over time, as well as prolactin and ferritin serum levels were evaluated at baseline (T0), 8-month follow-up (T8), and 16-month follow-up. The disability at T0, T8, and T16 was higher among patients with ProgMS than those with RRMS. Prolactin and ferritin levels did not differ over time between both groups. Initially, prolactin was associated with MS disability. After introducing age and sex, the effects of prolactin on disability were no longer significant. Prolactin was associated with age and sex, whereby age was positively associated with disability. In the same way, after introducing age and sex, the effects of diagnosis on prolactin levels, as well as the association between prolactin and ferritin, were no longer significant (P = 0.563 and P = 0.599, respectively). Moreover, 21.6% of the variance in the disability was predicted by age (P < 0.001), and sex (P = 0.049), while prolactin was not significant. In conclusion, the effects of prolactin on the disability and clinical forms of MS patients may be spurious results because those correlations reflect the positive associations of age with the disability and the negative association of age with prolactin.

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

No impact of treated hyperprolactinemia on cumulative live birth rate and perinatal outcomes in in vitro fertilization-embryo transfer.

AIM: To investigate whether treated hyperprolactinemia has an impact on pregnancy outcomes in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). METHODS: A retrospective cohort study was conducted on 535 women who underwent IVF/ICSI-ET between January 2012 and December 2016, of which 123 had treated hyperprolactinemia (case group), 369 were matched controls. Besides, 43 remained hyperprolactinemic after treatment consisted of abnormal group. Cumulative live birth rate (CLBR) after one oocyte retrieval cycle was taken as the primary outcome. A time-to-event analysis using Fine and Gray's test was used to compare CLBR between case and control groups. RESULTS: The median prolactin level was 80.00 ng/mL before dopamine agonist treatment in case group, and it reduced to 14.80 ng/mL after the treatment, similar to the level of control group (15.17 ng/mL, P = 0.316). No significant differences in baseline characteristics were found between case and control groups. The CLBR after one oocyte retrieval cycle were 69.1% (85/123) and 66.4% (245/369) in the case group and control group, respectively (P = 0.580). No significant differences were found between case and control groups in perinatal outcomes. Pregnancy and perinatal outcomes of abnormal group were similar to those of case and control groups. CONCLUSION: Impact of treated hyperprolactinemia on CLBR and perinatal outcomes in IVF-ET was not evident.

Hyperprolactinemic African elephant (Loxodonta africana) females exhibit elevated dopamine, oxytocin and serotonin concentrations compared to normal cycling and noncycling, low prolactin elephants†.

Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.

Hypothalamic-pituitary-gonadal axis dysfunction: An innate pathophysiology of schizophrenia?

The female hormone 17ß-estradiol is postulated to be protective against schizophrenia onset and severity. Hypoestrogenism is a common phenomenon in women with schizophrenia that has serious effects that adds to the burden of an already very onerous disease. The cause of hypoestrogenism is largely attributed to antipsychotic-induced hyperprolactinemia. Evidence suggest however that a significant portion of female schizophrenia patients develop hypoestrogenism either before antipsychotic treatment or without regard to the level of prolactin, suggesting that for a sizeable segment of female patients, gonadal abnormality may be an innate and early aspect of the disease. This review aims to summarise the available literature that examines gonadal dysfunction in schizophrenia through this prism as well as to outline some recent developments in treatment strategies that may provide feasible ways to successfully tackle hypoestrogenism in schizophrenia.

Prevalence and reproductive manifestations of macroprolactinemia.

PURPOSE: Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations. MATERIAL AND METHODS: Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical examination and hormone measurements besides CT/MRI for pituitary abnormalities. RESULTS: Prevalence of macroprolactinemia was 21.57% (22/102) in hyperprolactinemia (prolactin >100 ng/ml). There was no case of macroprolactinemia in physiological hyperprolactinemia, or healthy control females. Reproductive manifestations were present in 72.73% (16/22) macroprolactinemia cases, out of which macroprolactinemia was the sole cause of associated reproductive manifestations in 68.7% (11/16) cases. Reversal of reproductive dysfunction/s was observed in five cases with appropriate treatment for high macroprolactin. CONCLUSION: Macroprolactinemia prevalence was found to be 21.5%, out of which 72.73% cases had associated reproductive dysfunctions.

Effect of metoclopramide administration to mothers on neonatal bilirubin and maternal prolactin: a randomized, controlled, clinical trial.

BACKGROUND: Jaundice is a common neonatal problem. This study was conducted to determine the effect of metoclopramide on neonatal bilirubin and maternal prolactin (primary outcomes) and milk volume (secondary outcome). METHODS: This triple-blind, randomized, controlled, clinical trial was conducted on 112 mothers. The participants were assigned to the intervention (metoclopramide) and control groups (placebo) using block randomization. Ten-mg metoclopramide and placebo tablets were taken by the participants three times a day. The intervention began in the first 2-10 hours after childbirth and continued until the fifth day. The mothers' prolactin level was measured on the first morning after the intervention and on the sixth day (1 day after the intervention was over). Neonatal total bilirubin was also measured before the intervention and on the sixth day. RESULTS: After the intervention, the two groups did not differ significantly in terms of the mean neonatal indirect bilirubin (P = 0.565) and milk volume (P = 0.261), but the mean serum prolactin was significantly higher in the metoclopramide group compared to the placebo group (adjusted mean difference 37; 95% confidence interval 58.1-16.5; P = 0.001). CONCLUSIONS: Metoclopramide increased maternal serum prolactin but had no effects on neonatal jaundice. The insufficient numbers of studies on this subject mandate further research.

Clinical and Radiographic Characteristics Related to Hyperprolactinemia in Nonfunctioning Pituitary Adenomas.

OBJECTIVE: Hyperprolactinemia in patients with nonfunctioning pituitary adenomas (NFPAs) has been explained by the stalk compression of large pituitary adenomas. However, not all large NFPAs are associated with high serum prolactin levels. We aimed to elucidate and compare clinical, hormonal, and radiographic characteristics of NFPAs with and without hyperprolactinemia. METHODS: We included 201 patients with clinically NFPAs who underwent transsphenoidal surgery performed by a single surgeon during 2010-2017 at a single center in Korea. We measured the three-dimensional diameters (anteroposterior [AP], width, height) and volumes of NFPA on magnetic resonance imaging. We conducted morning basal hormone measurements and dynamic tests preoperatively and 3 months postoperatively. RESULTS: All NFPAs were macroadenomas, and mean tumor volume was 10.4 ± 7.7 cm3. Of 201 patients, 59 (29.4%) had preoperative hyperprolactinemia. Hormone recovery rate was higher in patients with hyperprolactinemia compared with patients without hyperprolactinemia after age, sex, body mass index, tumor volume, and gross total resection adjustments (odds ratio [95% confidence interval]: 2.55 [1.10-5.92]). Tumor width/AP diameter ratio positively correlated with serum prolactin levels (r = 0.186, P = 0.008). Tumor volume was not significantly different between the 2 groups. CONCLUSIONS: Preoperative prolactin level is a useful marker to predict hormone recovery after surgery. Patients with NFPA and hyperprolactinemia tended to have a higher width/AP diameter ratio. Hyperprolactinemia of NFPA is more likely affected by tumor growth pattern, such as width/AP diameter ratio, than tumor volume.

Antipsychotic-induced hyperprolactinaemia: case studies and review.

Antipsychotics are a known cause of hyperprolactinaemia and can be associated with significant health issues in short term and long term. The effects vary with gender and age of the individual and can contribute towards non-concordance and hence relapse in mental health of our patients. Clinicians need to educate the patients about this significant side effect of not only antipsychotic medications but other medications causing hyperprolactinaemia commonly prescribed in primary care.

Gynecomastia and hormones.

Gynecomastia-the enlargement of male breast tissue in men-is a common finding, frequently observed in newborns, adolescents, and old men. Physiological gynecomastia, occurring in almost 25 % of cases, is benign and self-limited; on the other hand, several conditions and drugs may induce proliferation of male breast tissue. True gynecomastia is a common feature often related to estrogen excess and/or androgen deficiency as a consequence of different endocrine disorders. Biochemical evaluation should be performed once physiological or iatrogenic gynecomastia has been ruled out. Non-endocrine illnesses, including liver failure and chronic kidney disease, are another cause of gynecomastia which should be considered. Treating the underlying disease or discontinuing medications might resolve gynecomastia, although the psychosocial burden of this condition might require different and careful consideration.

Consenso español sobre los riesgos y detección de la hiperprolactinemia iatrogénica por antipsicóticos / Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia

Introducción. La hiperprolactinemia iatrogénica (HPRLi) se ha descrito con más frecuencia con algunos antipsicóticos, dependiendo de su capacidad de bloqueo de los receptores de dopamina D2. Existe gran heterogeneidad de la práctica clínica y posiblemente falta de concienciación sobre este problema entre los médicos. Dada la elevada frecuencia con la que los pacientes con enfermedad mental grave reciben antipsicóticos de forma prolongada, se precisa vigilar posibles riesgos en su salud física. La HPRLi y sus síntomas pueden pasar desapercibidos si no se investigan rutinariamente. Metodología. Se realiza una revisión profunda de la literatura para elaborar un consenso multidisciplinario con psiquiatras junto a otros especialistas (de Endocrinología, Medicina Interna y Oncología) con el fin de consensuar los riesgos clínicos y los métodos de detección más adecuados de la HPRLi de acuerdo con los distintos niveles de evidencia científica (I-IV). Resultados. Los síntomas a corto plazo incluyen amenorrea, galactorrea y disfunción sexual (descenso del deseo y disfunción eréctil por hipogonadismo secundario). A medio-largo plazo y relacionado con la disminución de estrógenos, se pueden inducir baja masa ósea (osteopenia y osteoporosis), hipogonadismo, menopausia precoz, incremento del riesgo de algunos tipos de cáncer (mama y endometrio), aumento del riesgo cardiovascular, alteraciones en la inmunidad, dislipidemia y disfunción cognitiva, entre otros. La petición de niveles de PRL debería realizarse al inicio del tratamiento en todos los pacientes que reciben antipsicóticos, aunque no se observen síntomas precoces (amenorrea, galactorrea) por el riesgo de subestimar otros síntomas que pueden aparecen a medio plazo. Se aconseja determinar también niveles de FSL, LH, testosterona y vitamina D. Se recomienda explorar rutinariamente la función sexual, ya que puede ser un síntoma mal tolerado que podría conducir al abandono del tratamiento. Se propone un especial cuidado en niños y adolescentes, así como en pacientes con PRL > 50 ng/ml (intensidad moderada), revisando periódicamente si existe hipogonadismo o disfunción sexual. En los pacientes con PRL > 150 ng/ml debe descartarse siempre un prolactinoma radiológicamente y se debe prestar especial atención a posibles antecedentes de cáncer de mama o endometrio. Se aconseja realizar densitometrías en varones >50 años y en mujeres con amenorrea > 6 meses o menopausia precoz para detectar osteoporosis y evitar riesgo de fracturas por fragilidad (AU)

Introduction. Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. Methodology. An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). Results. Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50 ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150 ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old, amenorrhea > 6 months, or early menopause to avoid fracture risk (AU)

Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia. / Consenso español sobre los riesgos y detección de la hiperprolactinemia iatrogénica por antipsicóticos.

INTRODUCTION: Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. METHODOLOGY: An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). RESULTS: Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old, amenorrhea>6 months, or early menopause to avoid fracture risk.

[Current diagnosis and treatment of hyperprolactinemia]. / Diagnóstico y tratamiento actual de la hiperprolactinemia.

Hyperprolactinemia is a frequent neuroendocrinological condition that should be approached in an orderly and integral fashion, starting with a complete clinical history. Once physiological causes such as pregnancy, systemic disorders such as primary hypothyroidism and the use of drugs with dopamine antagonistic actions such as metochlopramide have been ruled out, the most common cause of hyperprolactinemia is a PRL-secreting pituitary adenoma or prolactinoma. Prolactinomas are usually classified as microprolactinomas (less than 1 cm) or macroprolactinomas (larger than 1 cm), which can either be confined or invasive. The hormonal consequence of hypeprolactinemia is hypogonadism; in women, this is manifested as amenorrhea/oligomenorreha, anovulation and galactorrhea, whereas in men the main complaints are a diminished libido and erectile dysfunction. Macroprolactinomas can also present with symptoms and signs resulting form mass effect of the tumor, such as headaches and visual field defects. Other structural causes of hyperprolactinemia include non-functioning pituitary adenomas and infiltrative disorders, which can interrupt the inhibitory, descending dopaminergic tone. The primary treatment of prolactinomas is pharmacological with dopamine agonists such as cabergoline.

La hiperprolactinemia es uno de los trastornos neuroendocrinológicos más frecuentes y su abordaje debe hacerse de manera ordenada e integral, partiendo de una historia clínica completa. Una vez excluidas las causas fisiológicas, como el embarazo, enfermedades sistémicas (como el hipotiroidismo primario) y el uso de fármacos con acción antidopaminérgica (como la metoclopramida), la causa más común de la hiperprolactinemia es la presencia de un adenoma hipofisario productor de prolactina (PRL) o prolactinoma. Los prolactinomas se clasifican por su tamaño en microprolactinomas (menores de 1 cm) y macroprolactinomas (mayores de 1 cm), los cuales a su vez pueden ser intraselares o invasivos. La consecuencia hormonal de la hiperprolactinemia es el hipogonadismo; en la mujer, esto se manifiesta como amenorrea/oligomenorrea, anovulación y galactorrea, mientras que en el hombre la manifestación consiste en la disminución de la libido y disfunción eréctil. En el caso de los macroprolactinomas, no es infrecuente encontrar síntomas y signos de efecto de masa como cefalea y alteraciones en los campos visuales. Otras causas estructurales de hiperprolactinemia son los adenomas no funcionantes y las enfermedades infiltrativas de la hipófisis, las cuales interrumpen el tono dopaminérgico descendente. El tratamiento primario de los prolactinomas es farmacológico, a base de agonistas dopaminérgicos, como la cabergolina.

Prevalence of conditions causing chronic anovulation and the proposed algorithm for anovulation evaluation.

AIM: This study investigated the prevalence of disease-causing chronic anovulation and proposes a logical investigation flowchart to facilitate diagnosis in women presenting with chronic anovulation. MATERIAL AND METHODS: The cross-sectional retrospective study was performed using 293 reproductive-aged women who were diagnosed with chronic anovulation at the Gynecologic Endocrinology Unit, Faculty of Medicine, Chiang Mai University between January 2008 and December 2012. The demographic data, laboratory investigations and diagnoses were collected. RESULTS: Among 293 patients recruited into the study, the common causes of anovulation were polycystic ovary syndrome (PCOS) (73.4%), prolactin disorder (13.3%) and unexplained chronic anovulation (7.5%). The less common causes were thyroid disorders, congenital adrenal hyperplasia, adrenal tumors and Cushing's disease. There was a strong positive association between the levels of 17-hydroxyprogesterone and/or dehydroepiandrosterone sulfate with the levels of testosterone and androstenedione. The sensitivity and specificity of serum luteinizing hormone to accurately diagnose PCOS were 29.38% and 55.56% (P = 0.03). The luteinizing hormone/follicle-stimulating hormone ratio ≥ 3 had a sensitivity and specificity at 18.56% and 92.86% (P = 0.03) for PCOS diagnosis. CONCLUSION: Serum androstenedione, testosterone, thyroid-stimulating hormone, prolactin levels and pelvic ultrasonography should be included in the initial investigations for anovulation. The 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels can be used for secondary anovulation evaluations.

Neuroendocrine causes of amenorrhea--an update.

CONTEXT: Secondary amenorrhea--the absence of menses for three consecutive cycles--affects approximately 3-4% of reproductive age women, and infertility--the failure to conceive after 12 months of regular intercourse--affects approximately 6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. OBJECTIVE: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. CONCLUSIONS: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception.

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...