Effect of Hyperprolactinemia on Bone Metabolism: Focusing on Osteopenia/Osteoporosis.

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) by a high prolactin level can result in decreased bone mineral density. Osteoporosis is a common skeletal disorder characterized by decreased bone mineral density (BMD) and quality, which results in decreased bone strength. In patients with hyperprolactinemia, changes in BMD can be induced indirectly by the inhibition of the GnRH-gonadal axis due to increased prolactin levels or by the direct action of prolactin on osteoblasts and, possibly, osteoclast cells. This review highlights the recent work on bone remodeling and discusses our knowledge of how prolactin modulates these interactions, with a brief literature review on the relationship between prolactin and bone metabolism and suggestions for new possibilities.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

The prevalence of thyroid dysfunction and hyperprolactinemia in women with PCOS.

Introduction: Ovulatory dysfunction is usually caused by an endocrine disorder, of which polycystic ovary syndrome (PCOS) is the most common cause. PCOS is usually associated with estrogen levels within the normal range and can be characterized by oligo-/anovulation resulting in decreased progesterone levels. It is suggested that decreased progesterone levels may lead to more autoimmune diseases in women with PCOS. In addition, it is often claimed that there is an association between hyperprolactinemia and PCOS. In this large well-phenotyped cohort of women with PCOS, we have studied the prevalence of thyroid dysfunction and hyperprolactinemia compared to controls, and compared this between the four PCOS phenotypes. Methods: This retrospective cross-sectional study contains data of 1429 women with PCOS and 299 women without PCOS. Main outcome measures included thyroid stimulating hormone (TSH), Free Thyroxine (FT4), and anti-thyroid peroxidase antibodies (TPOab) levels in serum, the prevalence of thyroid diseases and hyperprolactinemia. Results: The prevalence of thyroid disease in PCOS women was similar to that of controls (1.9% versus 2.7%; P = 0.39 for hypothyroidism and 0.5% versus 0%; P = 0.99 for hyperthyroidism). TSH levels were also similar (1.55 mIU/L versus 1.48 mIU/L; P = 0.54). FT4 levels were slightly elevated in the PCOS group, although within the normal range (18.1 pmol/L versus 17.7 pmol/L; P < 0.05). The prevalence of positive TPOab was similar in both groups (5.7% versus 8.7%; P = 0.12). The prevalence of hyperprolactinemia was similarly not increased in women with PCOS (1.3%% versus 3%; P = 0.05). In a subanalysis of 235 women with PCOS and 235 age- and BMI-matched controls, we found no differences in thyroid dysfunction or hyperprolactinemia. In according to differences between PCOS phenotypes, only the prevalence of subclinical hypothyroidism was significantly higher in phenotype B (6.3%, n = 6) compared to the other phenotypes. Conclusion: Women with PCOS do not suffer from thyroid dysfunction more often than controls. Also, the prevalence of positive TPOab, being a marker for future risk of thyroid pathology, was similar in both groups. Furthermore, the prevalence of hyperprolactinemia was similar in women with PCOS compared to controls.

The effect of antipsychotic medication and the associated hyperprolactinemia as a risk factor for periodontal diseases in schizophrenic patients: a cohort retrospective study.

BACKGROUND: Periodontal disease is a major health problem that results in tooth loss and thus affects oral health, which affects quality of life. In particular, schizophrenic patients are at higher risk for periodontal disease due to several factors, including the effect of antipsychotic medications received by those patients. Accordingly, the aim of the present cohort retrospective study is to explore the effect of antipsychotics on periodontal health and the possible effect of antipsychotic-induced hyperprolactinemia as a risk factor for periodontal disease progression in schizophrenic patients. METHODS AND OUTCOMES: The study population consisted of three groups: Group A (n = 21): schizophrenic patients that have been taking "prolactin-inducing" antipsychotics for at least 1 year; Group B (n = 21): schizophrenic patients who have been taking "prolactin-sparing" antipsychotics for at least 1 year; and Group C (n = 22): newly diagnosed schizophrenic patients and/or patients who did not receive any psychiatric treatment for at least 1 year. The study groups underwent assessment of periodontal conditions in terms of pocket depth (PD), clinical attachment loss (CAL), gingival recession, tooth mobility, and bleeding on probing (BOP). Also, bone mineral density was evaluated using DEXA scans, and the serum prolactin level was measured by automated immunoassay. RESULTS: Results revealed a statistically significant difference in PD, CAL, and serum prolactin levels (P ≤ 0.001, P = 0.001, and P ≤ 0.001, respectively) among the 3 study groups. For both PD and CAL measurements, group A has shown significantly higher values than both groups B and C, whereas there was no statistically significant difference between the values of groups C and B. Concerning serum prolactin levels, group A had significantly higher values than groups B and C (P ≤ 0.001 and P ≤ 0.001 respectively). There was a statistically significant difference (P ≤ 0.001) between the 3 study groups in terms of bone mineral density. Moreover, there was a statistically significant direct relation between serum prolactin level and other parameters including clinical attachment loss, pocket depth measurements and bone mineral density. CONCLUSION: According to our results, it could be concluded that all antipsychotics contribute to the progression of periodontal disease, with a higher risk for prolactin-inducing antipsychotics. However, further long term, large sampled, interventional and controlled studies are required to reach definitive guidelines to allow clinicians properly manage this group of patients.

Diagnostic workup of endocrine dysfunction in recurrent pregnancy loss: a cross-sectional study in Northeast China.

Objective: To evaluate the prevalence of abnormal endocrine dysfunction for recurrent pregnancy loss (RPL) amongst patients with two versus three or more pregnancy losses. Methods: This cross-sectional study retrospectively collected pre-pregnancy data of 537 women diagnosed with RPL in Shengjing Hospital of China Medical University from 2017 to 2022, including the baseline data of patients and the test results of endocrine factors. Several endocrine dysfunction included in this study were: thyroid dysfunction, obesity, hyperprolactinemia, polycystic ovary syndrome and blood glucose abnormality. Furthermore, vitamin D level were collected to study its relationship with endocrine dysfunction. Finally, we subdivided the patients according to the number of previous pregnancy loss and compared the prevalence of endocrine dysfunction between subgroups. Results: Among 537 RPL patients, 278 (51.8%) patients had abnormal endocrine test results. The highest incidence of endocrine dysfunction was thyroid dysfunction (24.39%, 131/537), followed by hyperprolactinemia (17.34%, 85/490), obesity (10.8%, 58/537), polycystic ovary syndrome (10.50%, 56/533), and abnormal blood glucose (5.29%, 27/510). Only 2.47%(13/527) of patients have vitamin D level that reach the standard. After subdividing the population according to the number of pregnancy loss, we did not find that the incidence of endocrine dysfunction (P=0.813), thyroid dysfunction (P=0.905), hyperprolactinemia (P=0.265), polycystic ovary syndrome (P=0.638), blood glucose abnormality (P=0.616) and vitamin D deficiency (P=0.908) were different among patients with two versus three or more pregnancy losses. However, obesity (P=0.003) was found more frequently observed in patients with more times of pregnancy loss. Conclusion: The prevalence of endocrine dysfunction in RPL population is high. There is no difference in the prevalence of endocrine dysfunction, except for obesity, among patients with two or more pregnancy losses, which may suggest investigations of endocrine dysfunction when patients have two pregnancy losses.

Hyperprolactinemia-induced acute ischemic stroke.

Strokes are the fifth leading cause of death in the United States with almost 800,000 patients seeking emergency care each year-most of whom are seen for ischemic strokes. Acute ischemic strokes (AIS) can be caused by emboli in diseases such as atrial fibrillation as well as thrombus formation in the form of platelet deposition in patients with atherosclerotic disease. Platelet activation by immunomodulators including thromboxane A2 (TXA2), serotonin, and thrombin have been extensively delineated; however, the activation by hormones such as prolactin has only recently been revealed. We present a case of a 25-year-old male with a history of pituitary microadenoma and hyperprolactinemia who presented with an acute ischemic stroke in the setting of medication non-compliance. To our knowledge, this is the first known case of AIS in a patient with known hyperprolactinemia who presented with a stroke due to be medication non-compliance.

Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men.

BACKGROUND: Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration. METHODS: We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded. RESULTS: Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median "low-HB duration" (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between "low-HB duration" and patient-reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The "low-HB duration" was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01). CONCLUSIONS: In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.

Prolactin-Raising and Prolactin-Sparing Antipsychotic Drugs and the Risk of Fracture and Fragility Fracture in Patients With Schizophrenia, Dementia, and Other Disorders.

Patients who require antipsychotic drug treatment are at increased risk of fractures, including osteoporosis-related fragility fractures, for reasons related to demographics, illness-related factors, and treatment-related factors. As examples, patients with dementia may be vulnerable to falls due to cognitive and psychomotor impairment, patients with schizophrenia may be vulnerable to injury related to physical restlessness or physical aggression, and patients receiving antipsychotics may suffer falls related to sedation, psychomotor impairment, bradykinesia, or postural hypotension. Antipsychotics may also increase the risk of fracture through long-term hyperprolactinemia and resultant osteoporosis. A meta-analysis of 36 observational studies conducted in mostly elderly samples found that antipsychotic exposure was associated with an increased risk of hip fracture as well as increased risk of any fracture; the findings were consistent in almost all subgroup analyses. An observational study that controlled for confounding by indication and illness severity found that fragility fractures in patients with schizophrenia were associated with higher daily doses, higher cumulative doses, longer duration of treatment, and prolactin-raising rather than prolactin-sparing antipsychotics; in patients receiving prolactin-raising antipsychotics, the concurrent use of aripiprazole appeared protective. The absolute risks of fracture are unknown and could vary depending on patient age, patient sex, indication for antipsychotic use, nature of the antipsychotic (and associated risk of sedation, psychomotor impairment, bradykinesia, and postural hypotension), daily dose prescribed, duration of antipsychotic exposure, baseline risk of fracture, and other risk factors. Patients should therefore be individually evaluated for risk factors for falls and fractures related to sociodemographic, clinical, and treatment-related risk factors. Patients identified to be at risk should be advised about risk-mitigating strategies. If prolactin-raising antipsychotics are required in the long term, prolactin levels should be monitored and prolactin-lowering strategies should be considered. Osteoporosis should be investigated and managed, if identified, to prevent fragility fractures.

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass. She was admitted to the Emergency Department (ED) and had findings of galactorrhea and hyperprolactinemia on examination. Imaging studies demonstrated a large ovarian mass measuring 15.0×9.0×18.8 cm that was resected, and subsequent pathology results showed JGCT stage 1A. CONCLUSIONS Prognosis of granulosa cell tumors (GCT) largely depends on its initial size, stage at diagnosis, residual tumors after surgery, and the subtype of GCT. If the patient is of reproductive age, fertility-sparing surgical options must be considered and patients must be regularly monitored for recurrence. JGCTs can present with minimal to no symptoms of precocious puberty in young girls but may present with amenorrhea, which may be considered normal for their developmental age. Although JGCTs are rare, they are important to include in differential diagnoses of younger female patients with abdominal pain, especially if accompanied by hormonal irregularities.

Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis?

PURPOSE: Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. METHODS: Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. RESULTS: Mean frontal bone thickness was 6.75 mm in acromegaly, 4.85 mm in group 1, and 5.1 mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. CONCLUSION: Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.

Effects of combined metformin and cabergoline versus metformin alone on ovarian and hormonal activities in Iraqi patients with PCOS and hyperprolactinemia: a randomized clinical trial.

Polycystic ovary syndrome (PCOS) is one of the most prevalent metabolic diseases during female reproductive life, often associated with insulin resistance and hyperprolactinemia. The efficacy of metformin and cabergoline for managing PCOS remains debated in the literature. This three-arm interventional study in Iraq assessed the effects of these drugs on body mass index (BMI), hormonal balance, and uterine artery blood flow in 75 women with PCOS and hyperprolactinemia. Participants were randomized into three groups: metformin (500 mg twice daily), cabergoline (0.5 mg weekly), and a combination of both, with 25 patients in each group. Baseline and 90-day follow-up characteristics included BMI, serum hormonal levels, and ultrasound features. Metformin resulted in significant weight reduction (p=0.038); however, the addition of cabergoline caused a more significant reduction in body mass index (p=0.001). The combined treatment significantly lowered testosterone levels (p=0.008). In addition, this combination significantly reduced the level of LH (p=0.043) and increased the level of FSH (p=0.047). The results suggest that metformin and cabergoline when used together, act synergistically and safely to reduce BMI, testosterone, and LH levels while increasing FSH levels. Furthermore, this combination improved endometrial blood flow and ovulation in women with PCOS.

The Effect of Prolactinoma on Tear Film Function.

Objectives: To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of hyperprolactinemia. Materials and Methods: Consecutive patients with prolactinoma and healthy controls were included in the study. Schirmer, tear break-up time (TBUT), tear osmolarity values, and ocular surface disease index (OSDI) scores were evaluated for each patient. Follow-up time and total duration of hyperprolactinemia were recorded for prolactinoma patients. Results: The study included 39 eyes of 39 patients with prolactinoma and 39 eyes of 39 age- and gender-matched healthy controls. Prolactinoma patients showed lower Schirmer (14.1±8.4 vs. 24.8±8.9 mm; p<0.001) and TBUT values (7.0±3.2 vs. 11.6±2.6 s; p<0.001) and higher OSDI scores (20.6±16.6 vs. 5.8±2.4; p<0.001) compared to the healthy controls. While the mean osmolarity of the prolactinoma patients was 301.6±8.3 mOsm/L, it was 297.7±12.5 mOsm/L for the healthy controls (p=0.07). The duration of hyperprolactinemia in prolactinoma patients showed a negative correlation with Schirmer (r=-0.395; p=0.013) and TBUT values (r=-0.377; p=0.018) and a positive correlation with OSDI scores (r=0.337; p=0.036). Conclusion: Prolactinoma patients had significantly lower Schirmer and TBUT levels and higher OSDI scores compared to the healthy controls, but no significant difference in tear osmolarity. The effect of high PRL levels on tear film function was duration-dependent.

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.

HETEROGENEITY OF CLINICAL MANIFESTATIONS OF HYPERPROLACTINEMIA (REVIEW AND OWN OBSERVATIONS).

The article is devoted to the features of the clinical picture of hyperprolactinemia, which can be partially determined by both gender and age of patients. Along with the well-known "classic" manifestations of hyperprolactinemiс syndrome, such as clinical signs of hypogonadism and mechanical pressure of the pituitary tumor on adjacent anatomical structures, there are others that are poorly known to a wide range of practicing physicians. Less frequent manifestations of hyperprolactinemia include the development of hypopituitarism, osteoporosis or osteopenia, alopecia. The analysis of literature data is illustrated with clinical examples from our own practice. It is noted that the pronounced heterogeneity of the clinical manifestations of hyperprolactinemia determines the need to develop continuity and consistency between doctors of different specialties for timely diagnosis and adequate treatment of this pathology.

Metabolic effects of prolactin.

Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic and lipid profiles, likely due to the suppression of physiologic dopaminergic tone. Prolactin receptors and dopamine receptors type 2 have been demonstrated to be expressed on both human pancreatic ß- cell and adipocytes, supporting a key role of prolactin and dopamine in peripheral metabolic regulation. Medical treatment with the dopamine agonists bromocriptine and cabergoline has been demonstrated to decrease the prevalence of metabolic syndrome and obesity, and significantly improve gluco-insulinemic and lipid profiles. In hyperprolactinemic men with concomitant hypogonadism, correction of hyperprolactinaemia and testosterone replacement has been proven to restore metabolic impairment. In turn, low prolactin levels have also been demonstrated to exert a detrimental effect on weight gain, glucose and lipid metabolism, thus leading to an increased prevalence of metabolic syndrome. Therefore, PRL values ranging from 25 to 100 mg/L, in absence of other recognizable pathological causes, have been proposed to represent a physiological response to the request for an increase in metabolic activity, and nowadays classify the so-called HomeoFIT- PRL as a promoter of metabolic homeostasis. The current review focuses mainly on the effects of hyperprolactinemia and its control by medical treatment with DAs on the modulation of food intake, body weight, gluco-insulinemic and lipid profile. Furthermore, it provides the latest knowledge about the metabolic impact of hypoprolactinemia.

Metabolic effects of prolactin and the role of dopamine agonists: A review.

Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and metabolism. Elevated prolactin levels are widely associated with worsening metabolic disease, but it appears that low prolactin levels could also be metabolically unfavorable. This review discusses the pathophysiology of prolactin related metabolic changes, and the less commonly recognized effects of prolactin on adipose tissue, pancreas, liver, and small bowel. Furthermore, the effect of dopamine agonists on the metabolic profiles of patients with hyperprolactinemia are discussed as well.

Mild hyperprolactinemia in a couple: What impact on fertility?

Mild-to-moderate hyperprolactinemia is a frequent finding in young women presenting with infertility. Prolactin (PRL) concentration should be determined accurately, whether or not the patient has other symptoms suggestive of excess PRL such as galactorrhea or menstrual cycle disorder. After confirmation of persistent hyperprolactinemia on a second blood sample (avoiding conditions known to raise prolactin) and exclusion of macroprolactinemia, prolactinoma and other identifiable non-tumoral causes of hyperprolactinemia must be ruled out. Mildly elevated PRL levels may cause luteal insufficiency in cycling women and are associated with recurrent miscarriage. Any confirmed hyperprolactinemia should be treated in a woman who wishes or fails to become pregnant. Preference is given to cabergoline at the lowest possible dose that normalizes PRL, restoring fertility in the vast majority of cases. Evidence is much less robust in men, in whom PRL concentrations are less prone to increase and the reproductive system is less sensitive to the negative effects of hyperprolactinemia. Nevertheless, chronic and significant hyperprolactinemia in men may impair fertility or cause infertility (with or without hypogonadism) and must be treated, as in women. However, more clinical studies are clearly needed concerning male reproductive function. The significance of mild but persistent hyperprolactinemia in either member of a couple incidentally discovered during assisted reproductive technology (ART) procedures is unclear, and future evidence-based studies are needed to determine whether normalizing prolactin can improve ART outcome.

Bromocriptine therapy: Review of mechanism of action, safety and tolerability.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs.