Search

Dihydropteridine reductase (DHPR) deficiency is a disorder that prevents regeneration of tetrahydrobiopterin (BH4), causing hyperphenylalaninemia (HPA) and low levels of neurotransmitters, including dopamine. Due to low levels of dopamine, patients present with hyperprolactinemia. Treatment consists of a phenylalanine (Phe)-restricted diet, hydroxytryptophan and levodopa (L-Dopa) supplementation, leading to a rapid normalization of prolactin (PRL) levels. We report a case of a patient with DHPR deficiency presenting with new symptomatic hyperprolactinemia and amenorrhea in adolescence despite appropriate management. The prolactinoma was confirmed with pituitary magnetic resonance imaging. The patient was started on cabergoline with rapid normalization of PRL levels and resolution of symptoms, in keeping with previous reports. Cabergoline has a stronger affinity for the D2R receptor and longer half-life than L-Dopa, leading to lactotroph apoptosis, tumor shrinkage, and rapid and maintained normalization of PRL levels, with a better side-effect profile. Patients with DHPR deficiency need to be actively monitored for symptomatic hyperprolactinemia, as L-Dopa monotherapy is insufficient to suppress PRL secretion, leading to lactotroph hypertrophy and proliferation over time and development of prolactinomas in later life. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of the dopamine agonist cabergoline in uncontrolled acromegaly despite long-acting somatostatin analog (SSA). Methods: Thirty-five patients with acromegaly who were followed up in the department of endocrinology and metabolism of our university were analyzed. Thirty-five patients with acromegaly who did not respond adequately to postoperative SSA and in whom cabergoline was added to the treatment were analyzed. Patients were retrospectively evaluated in terms of age, gender, insulin-like growth factor-1 (IGF-1) values before and after cabergoline, disease duration, treatment dose, adenoma size, growth hormone level, and prolactin staining on pathologic examination. Results: Seventeen (48.6%) patients were female. The median age was 46.0 (41-53) years, and the median disease age was 10 (3-43) years. Twenty-eight (80.0%) were macroadenomas, 7 (20.0%) were microadenomas, and prolactin staining was observed in 10 (27.8%) cases. The IGF-1 level was 443 (346-628) ng/mL before cabergoline treatment and 27.4% decrease in IGF-1 was observed after treatment (p<0.001). There was no correlation between IGF-1 decrease and cabergoline dose. The change in IGF-1 was not correlated with tumor size and age but was correlated with pre-cabergoline IGF-1 level (r=0.364, p=0.03). 8 (22.9%) patients went into remission with cabergoline treatment. There was no difference in age, gender, tumor size, or pre-treatment IGF-1 levels between those who went into remission with cabergoline treatment and those who did not. When these 8 patients were analyzed, it was observed that cabergoline treatment was continued throughout the follow-up period; remission was maintained in one patient by discontinuing SSA treatment, in three patients by decreasing the SSA dose, in two patients without treatment change, and in two patients by changing the SSA preparation. Conclusion: Cabergoline is used in the treatment of acromegaly due to its antiproliferative and proapoptotic effects on pituitary adenoma cells. The efficacy of cabergoline added to SSA treatment is controversial in the literature. In our study, remission was achieved in 22.9% and IGF-1 reduction was observed in 27.4% with cabergoline treatment in patients with inadequate response to SSA treatment. Cabergoline added to SSA is an effective treatment in terms of IGF-1 control. This effect may continue in the long-term. [ABSTRACT FROM AUTHOR]

• OHSS is a common complication following controlled ovarian hyperstimulation during ART. • Calcium infusion and cabergoline have been shown to reduce the severity of OHSS. • This first-ever meta-analysis comprised six studies with 1687 patients. • Calcium infusion and cabergoline yielded similar pregnancy-related outcomes. • Calcium infusion could be more effective than cabergoline in reducing the rate of severe OHSS. To conduct the first-ever systematic review and meta-analysis evaluating calcium infusion versus cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) among high-risk women undergoing assisted reproductive technology. Six databases were screened from inception until April 1, 2024. The included randomized and non-randomized controlled studies were assessed for quality. The endpoints included the severity of OHSS and selected pregnancy-related outcomes. Endpoints were summarized as risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. Six studies were analyzed, including 1687 patients (828 in the calcium group and 859 in the cabergoline group). The quality of the studies varied and reflected low risk and high risk of bias in two and four studies, respectively, according to the revised Cochrane risk of bias tool. No significant differences were noted between both groups regarding the rates of overall (n = 5, RR = 0.65, 95 % CI [0.39, 1.07], p = 0.09), mild (n = 4, RR = 1.05, 95 % CI [0.59, 1.89], p = 0.86), moderate (n = 5, RR = 0.41, 95 % CI [0.15, 1.08], p = 0.07), and severe (n = 6, RR = 0.36, 95 % CI [0.11, 1.22], p = 0.1) cases of OHSS. Leave-one-out sensitivity analysis of an outlier study revealed that calcium significantly reduced the occurrence of severe OHSS compared with cabergoline (n = 5, RR = 0.16, 95 % CI [0.09, 0.43], p < 0.001, Higgins I2 = 0 %). No significant differences were observed between both groups regarding the rates of clinical pregnancy (n = 4, RR = 0.97, 95 % CI [0.88, 1.07], p = 0.57), ongoing pregnancy, live birth, and spontaneous abortion (Higgins I2 < 50 % for all). Both agents yielded similar pregnancy-related outcomes. However, calcium infusion could potentially be more effective than cabergoline in reducing the rate of severe OHSS. Additional high-quality and well-controlled trials are essential to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Background: Uterine fibroids are one of the most common benign tumors that cause abnormal bleeding and pain in women of reproductive age. One of the objectives of this study is to evaluate the effect of cabergoline drug on the size and volume of uterine bleeding as well as menopausal symptoms in women with uterine myomas. Methods: This double-blind clinical trial was conducted among 80 women with fibroid myomas and Abnormal Uterine Bleeding (AUB). The participants were allocated to two groups after random allocation. Group I received Cabergoline, 1 tablet (0.5 mg/w) orally once a week for 3 months. Group II obtained a placebo tablet (0.5 mg/w), taken at the same time. Results: 80 patients were included in the study (40 patients in the control group and 40 patients in the cabergoline treatment group). No statistically significant difference was observed between the two groups in terms of age, number of pregnancies, number of births, body mass index, uterine myoma characteristics, myoma type, myoma volume, and myoma number. A 37% decrease in myoma size was observed in the cabergoline recipients, as well as a 25% decrease in the placebo group, which is not statistically significant (p-value >0.05). Conclusion: Cabergoline drug reduces the volume of bleeding and the number of uterine myomas, but this reduction is not statistically significant and requires more studies in this field. [ABSTRACT FROM AUTHOR]

Introduction: : Pituitary apoplexy (PA) is a rare clinical syndrome due to acute/subacute pituitary hemorrhage and/or infarction; data on PA in functioning pituitary adenoma (FPA) is scarce. Methods: A retrospective record-review of details of PA in non-functioning (NFPA) and FPA managed at tertiary endocrine center. Results: 93 patients [56 males; 33.3% FPA: 5 acromegaly, 14 prolactinoma, and 12 Cushing's Disease (CD)] diagnosed with PA were included. Median age was 40 years, with younger age of presentation in FPA. Type A (acute) [49.5%] and headache (78.5%) were the commonest presentations, with PA being the initial manifestation in 98.4% of NFPA. Median (range) Pituitary Apoplexy Score (PAS) was 2 (0–8). Median tumor diameter was 2.5 cm, with larger tumors in FPA (3.2 cm vs. 2.3 cm). 29 (46.7%) NFPA-PA and 14 (45.2%) FPA-PA patients [71% prolactinoma, 33% in CD, and none in acromegaly] were conservatively managed. In the NFPA cohort, those managed surgically had significantly higher PAS (4 vs. 1) and larger tumor size (2.6 vs. 1.8 cm); however, both arms had comparable recovery of neuro-visual, radiological, and hormonal outcomes. In FPA cohort, CD and acromegaly required definitive treatment, whereas prolactinomas were effectively managed (clinical and biochemical recovery) with oral cabergoline and glucocorticoids. Matching PAS cohorts (to overcome allocation bias for management approach) in macroadenomas (excluding prolactinoma) showed comparable neuro-deficit and hormonal recovery between surgical and conservative approaches. Conclusion: PA in FPA has distinct features and management issues. Carefully selected patients (PAS guided) in NFPA with PA for conservative management have comparable outcomes to surgery. [ABSTRACT FROM AUTHOR]

Background: Metformin plays a major part in the treatment of polycystic ovarian syndrome.Trials are being conducted to compare the effectiveness of combination of metformin with cabergoline in the treatment of hyperprolactinemia and polycystic ovarian syndrome. Objectives: The purpose of this study is to compare the effectiveness of metformin monotherapy and combination therapy with cabergoline versus metformin for the management of polycystic ovarian syndrome with hyperprolactinemia. Methodology: An extensive search up until 31 May 2024 of electronic databases (PubMed, Registry of Controlled Clinical Trials, Web of Sciences, SCOPUS) to find pertinent studies. An analysis was conducted with both observational data and randomized clinical trials. To compute the standard mean difference, weighted mean difference, odds ratio, and 95% confidence interval, RevMan (v5.3) was utilized. Primary outcomes that were assessed included body-mass index, regular menstruation, weight change, prolactin, testosterone, and dehydroepiandrosterone-sulfate levels. Results: Three randomized controlled trials and 1 observational study, taking a total patient population of n = 535, were part of our final analysis. Prolactin (SMD = −3.23 95% CI: (−4.90, −1.55)) and dehydroepiandrosterone-sulfate levels (SMD = −0.27 95% CI: (−0.52, −0.01)) were significantly lower in the metformin and cabergoline combination therapy group; monthly regularity was also significantly higher (OR = 3.07 95% CI: (2.09, 4.51)). Statistically, there was no significant difference in weight, body-mass index, or testosterone levels. Conclusions: In the treatment of polycystic ovarian syndrome, the combination of metformin and cabergoline significantly lowers prolactin levels and encourages regular menstrual cycles. Although metformin has the potential to suppress testosterone levels, more investigation is required to determine how combination therapy affect dehydroepiandrosterone-sulfate and testosterone levels. It's interesting to note that while neither intervention had a substantial impact on weight or body-mass index, metformin and cabergoline combination therapy outperformed metformin monotherapy in terms of supporting regular menstrual cycles. Customized therapy approaches are essential, and large-scale trials involving a variety of groups are required to comprehend the safety and effectiveness of treatments. Plain language summary: Efficacy of metformin compared to metformin and cabergoline combination In this study, 2 therapies for women with high prolactin levels—a hormone associated with PCOS—were examined. Their goal was to determine which combination of metformin and cabergoline produced the best results.Observational data and randomized clinical trials were included while searching through several databases for pertinent studies. Researchers discovered that the combination of metformin and cabergoline was superior to using metformin alone in reducing prolactin and another hormone called DHEAS. The menstrual periods of women receiving the combined therapy were also more regular. However, there wasn't much difference in weight, body mass index (BMI), or testosterone levels between the 2 groups. In summary, it appears that the combination of cabergoline and metformin is a more effective way to treat the symptoms of PCOS, which include irregular periods and elevated prolactin levels. To find out how it impacts other hormones and whether it's long-term safe and effective, further research is still required. [ABSTRACT FROM AUTHOR]

The present study was conducted in the twenty-eight number of bitches aged between 2 to 6 years presented to SAC-OP-OG unit of Madras Veterinary College Teaching Hospital with a history of inappetence, lethargy, polyuria, polydipsia and distended abdomen which was further confirmed as pyometra by radiography and ultrasound examination. Further, the bitches were divided equally into group I and II. Group I (n=14) was treated with Tab. Mifepristone @ 2.5 mg/kg b.wt. per OS, Tab. Cabergoline @ 5 µg/kg b.wt. per OS and Tab. Misoprostol @ 100 µg per vaginum for 7 to 14 days. Group II (n=14) bitches directly underwent ovariohysterectomy. The assessment of uterine distention was performed by follow-up ultrasonography on day 7, 14, 21 and 28. The blood samples were collected on day 0 (before administering treatment) and on day 7, 14 and 21 in both groups for haemato-biochemical examination. In Group I, 78.57% and 63.63% of cases responded and conceived, respectively, in next cycle, while 9.09% cases had recurrence of pyometra. The altered haemato-biochemical indices in Group I and II were reversed between 14 to 21 and 7 to 10 days, respectively. The study concluded that the physiological and haemato-biochemical reversal is delayed in Group I with ovariohysterectomy, but mifepristone and cabergoline used in Group I prove to be safe and efficient therapeutic protocol for management of closed pyometra and restoring the breeding ability in young bitches. [ABSTRACT FROM AUTHOR]

Copyright of Hamidiye Medical Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

Hyperprolactinemia has multiple etiologies and is the most common endocrine manifestation of pathology of the hypo­thalamic-pituitary axis. Hyperprolactinemic hypogonadism is of great scientific interest due to the prevalence of endocrine pathology in the reproductive period and its effect on metabolic processes. Hyperprolactinemia is one of the serious obstacles to the implementation of reproductive function in both women and men. The article discusses current issues of diagnosis and management tactics for patients with hyperprolactinemia of various etiologies within the framework of preconception preparation.

Introduction: Global obesity rates are rising due to rapid urbanisation and sedentary lifestyles, affecting health and economics. Modifications to one's way of life, medical interventions, and surgical procedures are among the methods that can be utilised to manage obesity. New dopaminergic drugs show promise, but regulatory hurdles remain. Dopamine modulation may reduce metabolic dysfunctions, but more research is needed. Aim and objectives: This study aims to examine the impact of Cabergoline on glucose tolerance and weight in obese adults. Method: The impact of cabergoline on blood glucose levels was examined in a double-blind research including 120 obese patients who were given either the active ingredient or a placebo. There was no statistically significant difference seen between the groups (P = 0.792). Medications were delivered every week for 3 months in addition to the ongoing therapy. The study involved the implementation of fundamental laboratory tests and measures to continuously monitor the outcomes. Result: This study presents the initial characteristics of the Cabergoline and Control groups, and compares them at 3 and 6 months. There were no notable disparities observed in terms of weight, waist circumference, blood pressure, or BMI. Once more, it examines the laboratory attributes before and following a 3-month therapy period, revealing that there are no notable disparities between the Cabergoline and Control groups in the majority of measures. Conclusion: Cabergoline did not differ significantly from the control group in terms of weight, waist circumference, blood pressure, body mass index (BMI), or the majority of laboratory values after three months. [ABSTRACT FROM AUTHOR]

• PCOS and hyperprolactinemia are well known to co-exist. • Metformin and cabergoline, can provide additional benefits when given together. • Prolactin levels along with other hormonal profile seems to get benefit from this combination. • BMI also exhibits positive responses to this combined therapy. Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive years. Metformin (MET) has been shown to improve ovarian function in PCOS-related conditions, while cabergoline is recognized for its powerful and sustained ability to reduce prolactin levels. This study investigates the potential impact of combining cabergoline with metformin while comparing it with metformin alone in the treatment of PCOS alongside hyperprolactinemia. To gather data, we searched PubMed, Google Scholar, ScienceDirect, and Cochrane Central. Eligible studies were randomized controlled trials involving patients with PCOS and hyperprolactinemia. Outcome measures included changes in the levels of prolactin, testosterone, DHEAS, BMI and menstrual irregularities. RevMan version 5.4 was used to analyze outcomes. This study incorporated three Randomized Controlled Trials (RCTs) involving 405 participants in total. Patients receiving a combination of metformin and cabergoline experienced significant reductions in prolactin and testosterone levels (p= <0.0001 and p=<0.0001, respectively). Conversely, alterations in DHEAS levels and BMI did not reach statistical significance (p = 0.19 and p = 0.71, respectively). Notably, women solely prescribed metformin exhibited significantly higher rates of menstrual irregularities compared to those receiving both metformin and cabergoline (p=<0.0001). Our analysis underscores the synergistic effect achieved by pairing metformin and cabergoline in patients with PCOS and hyperprolactinemia. However, we encountered only a restricted number of studies meeting our criteria. It is imperative to consistently assess the combined effects of metformin and cabergoline to gain deeper insights into their effectiveness in addressing PCOS and hyperprolactinemia. [ABSTRACT FROM AUTHOR]

Purpose: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). Methods: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018–2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. Results: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. Conclusions: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed. [ABSTRACT FROM AUTHOR]

Background: Mastalgia, or breast pain (or mastodynia), is globally a common symptom experienced by women of reproductive age; treatment for these conditions is not yet standardized. Most of the drugs used for mastalgia are expensive and have side effects, so, the aim of this study was to compare different agents for reducing mastalgia in fibrocystic disease of women in outpatient clinics at Zagazig University. Methods: this prospective random comparative study has been carried out in Zagazig University out patients clinics specifically in breast clinic subjects in period between May-2019 to March -2020 on 68 patients enrolled with 3 months period of follow up. Results: In EPO group 30% of patients showed complete resolution and 61% showed partial response. The danazol group received, 58% of patients showed complete resolution and 41% showed partial improvement. In Tamoxifen group 47% of patients showed complete resolution while 52 % showed partial improvement. In the cabergoline group 14% of patient showed complete resolution and 42% showed partial improvement. Conclusions: Evening prime rose oil is effective in reducing the severity of mastalgia with minor tolerable side effects and should be used as first line of management. Danazol is the most effective agent but its side effects make it less favorable agent. Tamoxifen is the second most effective agent among the other agents with reversible tolerable side effects. Cabergoline is significantly decrease breast pain especially cyclic mastalgia, with notable side effects. [ABSTRACT FROM AUTHOR]

In the present work, simple method was utilized for the preparation of two-dimensional Ni-metal organic framework nanosheets (2D Ni-MOF NSs). Characterization techniques, including Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and field-emission scanning electron microscopy (FE-SEM) were applied to characterize the as-prepared 2D Ni-MOF NSs. Then, carbon paste electrode (CPE) modified with 2D Ni-MOF NSs and ionic liquid (IL) was used as sensing platform for voltammetric determination of levodopa. A considerable enhancement in the current response of levodopa was observed at the 2D Ni-MOF NSs/ILCPE compared to other CPEs. After optimization of conditions, the current response recorded at 2D Ni-MOF NSs/ILCPE linearly increased with an increase in levodopa concentration in the range from 0.09 to 365.0 µM, corresponding to a limit of detection of 0.03 µM. Also, the developed sensor showed significant electrocatalytic activity toward the oxidation of levodopa and cabergoline and provided two well-separate oxidation peaks to determine levodopa and cabergoline simultaneously. Moreover, the 2D Ni-MOF NSs/ILCPE presented good and efficient practicability with satisfactory recoveries (97.3–104.6%) and low RSD values of less than 3.6% for the determination of levodopa and cabergoline in real samples. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are known as antigen‐presenting cells that are capable of regulating immune responses. DCs and T cells can interact mutually to induce antigen‐specific T‐cell responses. Cabergoline, which is a dopamine (DA) receptor agonist, seems to implement anti‐inflammatory properties in the immune system, and therefore in the present study the impact of a DA receptor agonist cabergoline on the monocyte‐derived DCs (moDCs) was assessed. Immature moDCs were treated with lipopolysaccharide to produce mature DCs (mDCs). The expression of DCs' related surface markers namely: CD11c, HLA‐DR, and CD86 was measured by utilizing of flow cytometry. Real‐time PCR was the technique of choice to determine the levels at which diverse inflammatory and anti‐inflammatory factors in cabergoline‐treated and control mDC groups were expressed. DCs treated with cabergoline displayed a significant decrease in CD86 and HLA‐DR expression, markers linked to maturation and antigen presentation, respectively. In addition, the cabergoline‐mDC group showed a considerable decline in terms of the levels at which IL‐10, TGF‐β, and IDO genes were expressed, and an increase in the expression of TNF‐α and IL‐12 in comparison to the mDC control group. Our findings revealed that cabergoline as an immunomodulatory agent can relatively shift DCs into an immunogenic state, and there is a requirement for further investigations to evaluate the effects of cabergoline‐treated DCs on the T cell responses in vitro, and also in various diseases including cancer in animal models. Significance statement: Cabergoline‐mediated dopamine receptor provoking in the monocyte‐derived dendritic cells (DCs) significantly decreased CD86 and HLA‐DR expression, markers linked to maturation and antigen presentation, respectively. Furthermore, it could downregulate the expression of IL‐10, TGF‐β, and IDO genes, and upregulate the expression of TNF‐α and IL‐12 genes. Our findings revealed that cabergoline as an immunomodulatory agent can shift DCs into a partially immunogenic state. [ABSTRACT FROM AUTHOR]

Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old man who presented with overt Cushing syndrome. Morning blood cortisol, ACTH, 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and bedtime salivary cortisol were highly variable, reaching markedly elevated values. Intravenous desmopressin administration produced no ACTH or cortisol increase. Pituitary magnetic resonance imaging, thoracic computed tomography, and DOTATATE positron emission tomography scan identified no lesion. Inferior petrosal sinus sampling (IPSS) with desmopressin stimulation resulted in elevated central-to-peripheral ACTH ratio and prolactin co-secretion, while peripheral ACTH remained stable. No corticotroph tumor was identified on pituitary surgery pathology. Hypercortisolism persisted postoperatively. Cabergoline was initiated, after which the patient rapidly developed transient severe adrenal insufficiency (AI). Bilateral adrenalectomy was performed in view of persistent hypercortisolism. This is an unusual case of petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, desmopressin should still be used during IPSS in patients with no peripheral response. It is unclear whether the AI episode resulted from a combination of nadir of cyclic hypercortisolism, partial apoplexy, and response to cabergoline of an occult corticotroph tumor. [ABSTRACT FROM AUTHOR]

Objective Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells. Design and Methods Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape. Results Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples. Conclusions Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG. [ABSTRACT FROM AUTHOR]

Objective The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). Design This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. Methods Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. Results Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P <.01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P =.03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P <.01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P =.04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. Conclusion In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients. [ABSTRACT FROM AUTHOR]

Purpose: Prolactin (PRL)-secreting tumours are associated with infertility and can be reverted by dopamine agonist (DA) therapy. The suspension of DA is recommended once pregnancy is established, as all DAs cross the placenta. The aim of the study was to evaluate the rate of maternal-foetal complications in women treated with cabergoline (CAB) or bromocriptine (BRM) for prolactinoma during gestation and the effect of pregnancy on prolactinoma progression. Methods: This was a retrospective observational study involving 43 women affected by prolactinoma who became pregnant during therapy with CAB or BRM for a total of 58 pregnancies. For each patient, medical records were analysed by integrating the data with outpatient or telephone interview. Results: At the time of conception, 18 women were in the BRM group, while 40 were in CAB group. No differences were found in obstetric or neonatal outcomes between the two groups. There was a significant difference (p = 0.046) in child complications reported in maternal interview found exclusively in the CAB group. No further confounding factors were detected. Disease remission rate after the first pregnancy was 42.9% and the main predictor was a lower PRL nadir before pregnancy (p = 0.023). No difference was detected between the two groups in terms of tumor remission. Breastfeeding did not modify the outcome. Conclusion: Foetal exposure to DAs during the first weeks of embryogenesis is not associated with a greater risk of complications. The transient and mild developmental disorders recorded resolved spontaneously and the prevalence was substantially overlapping with that observed in the general population. [ABSTRACT FROM AUTHOR]

Background: Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have been used to improve our fundamental understanding of TMS-induced synaptic plasticity. Methods: We systematically reviewed the literature pairing pharmacological adjuncts with TMS plasticity-induction protocols in humans. We searched MEDLINE, PsycINFO, and Embase from 2013 to Mar. 10, 2023. Studies published before 2013 were extracted from a previous systematic review. We included studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. Results: Thirty-six studies met our inclusion criteria (28 in healthy and 8 in clinical populations). Most pharmacological agents have targeted the glutamatergic N-methyl-D-aspartate (NMDA; 15 studies) or dopamine receptors (13 studies). The NMDA receptor is necessary for TMS-induced plasticity; however, sufficiency has not been shown across protocols. Dopaminergic modulation of TMSinduced plasticity appears to be dose-dependent. The GABAergic, cholinergic, noradrenergic, and serotonergic neurotransmitter systems have small evidence bases supporting modulation of TMS-induced plasticity, as do voltage-gated calcium and sodium channels. Studies in clinical populations suggest that pharmacological adjuncts to TMS may rescue motor cortex plasticity, with implications for therapeutic applications of TMS and a promising clinical trial in depression. Limitations: This review is limited by the predominance in the literature of studies with small sample sizes and crossover designs. Conclusion: Pharmacologically enhanced TMS largely parallels findings from ex vivo preparations. As this area expands and novel targets are tested, adequately powered samples in healthy and clinical populations will inform the mechanisms of TMS-induced plasticity in health and disease., Introduction Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation technique that induces electrical currents in underlying brain parenchyma through electromagnetic induction. (1) It is one of the most established noninvasive [...]

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Objective: Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur afteradministration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule withanti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model ofOHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictorproteins and ovarian histological changes in an experimental OHSS rat model.Materials and Methods: In this experimental study, 30 adult female rats (two months old) were randomly divided intosix groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days),iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascularendothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone(P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes.Results: Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atreticfollicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of theVEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantlyattenuated all molecular and histological alterations observed in the OHSS animals.Conclusion: Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patientsby reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings aresimilar to CAB and can be a new avenue for future research on BET.

Abstract Background Acute retinal pigment epitheliitis (ARPE) is a rare, idiopathic and self-limiting disease. The article aims to present ARPE in a patient using D2 dopamine receptor agonists for the treatment of hyperprolactinemia. Case presentation A 28-year-old female during hyperprolactinaemia treatment suffered from a dyschromatopsia and a central visual field defect in the left eye. She noticed a deterioration of vision and discontinued the cabergoline administration. The woman had not been diagnosed with other chronic conditions and exhibited no symptoms of infection. Upon admission, the patient was subjected to a test for COVID-19, which was negative. The ophthalmological examination revealed a decrease in visual acuity to distance in the left eye, which amounted to 18/20 on the Snellen chart. A central scotoma was noted on the Amsler chart and a loss of pigment epithelium was visible on the fundus of the left eye. Fluorescein angiography showed a discrete window defect in the left one, with no signs of leakage. Optical coherence tomography (OCT) scans of the maculae revealed a characteristic change in the photoreceptor layer and retinal pigment epithelium (RPE) in the fovea in the left eye. The electrophysiological tests revealed decreased function of cells in macular region. A magnetic resonance imaging (MRI) of the head and orbits demonstrated an asymmetric pituitary gland without chiasm compression and discrete signal enhancement from the left optic nerve. The patient underwent observation during hospitalisation. She reported improved colour vision and a decreased scotoma in the centre of her visual field. In regular outpatient follow-ups, successive improvements in visual acuity, as well as a decreased RPE damage and outer photoreceptor layer loss during an OCT test were observed. Conclusions A case of ARPE is reported in a patient taking medications for hyperprolactinemia. The role of dopamine receptor antagonists in the photoreceptor function and causation of ARPE needs further evaluation.

Objective: Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur after administration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule with anti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model of OHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictor proteins and ovarian histological changes in an experimental OHSS rat model. Materials and Methods: In this experimental study, 30 adult female rats (two months old) were randomly divided into six groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by 30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days), iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone (P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes. Results: Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atretic follicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of the VEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantly attenuated all molecular and histological alterations observed in the OHSS animals. Conclusion: Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patients by reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings are similar to CAB and can be a new avenue for future research on BET. [ABSTRACT FROM AUTHOR]

Rationale: Cabergoline (CAB) is an ergot derivative typically prescribed for the treatment of hyperprolactinemia. It suppresses the release of prolactin through agonist actions on dopamine (DA) D2 receptors; however, it possesses binding affinity for other DA and 5-HT receptors. Side effects that exacerbate valvular heart disease can occur with high doses. Objective: The present study examined the acute, subchronic, and chronic dose–response effects of CAB and a derivative dimethylcabergoline (DMC) which acts as an antagonist instead of agonist at 5-HT 2B receptors, on appetitive and consummatory sexual behaviors of male rats. Methods: CAB (0, 0.03, 0.15, or 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 68 days. Sexual behavior was tested every 4 days during this period for a total of 16 trials. On the 17th trial, rats were administered their dose of CAB, and 4 h after were overdosed with sodium pentobarbital, perfused intracardially, and their brains processed for Fos immunohistochemistry. DMC (0, 0.03, 0.15, 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 36 days. Sexual behavior was tested every 4 days for a total of 9 trials. Results: CAB increased anticipatory level changes, intromissions, and ejaculations significantly across all timepoints, with the medium and high doses being most potent. The medium and high doses also increased Fos protein significantly within the medial preoptic area, whereas in the nucleus accumbens shell, the low and medium doses decreased Fos protein but the high dose increased it significantly from control. Similar to CAB, the medium and high doses of DMC increased the number of ejaculations significantly. Rats in all drug dose groups appeared healthy for the duration of the experiments. Conclusions: Both CAB and DMC facilitate ejaculations, and CAB further facilitates measures of anticipatory sexual motivation and intromissions. These data suggest that both could be used as treatments for sexual arousal disorders and ejaculation/orgasm disorders with little or no untoward side effects at low doses. [ABSTRACT FROM AUTHOR]

Background: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. Objective: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). Methods: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. Result: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88–0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03–0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37–42.97, p 0.021). Conclusion: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder. [ABSTRACT FROM AUTHOR]

Objective When transsphenoidal surgery (TSS) does not cure Cushing's disease (CD), 4 treatments are available: drug treatment (DT), second TSS (2nd TSS), bilateral adrenalectomy (BA), and pituitary radiotherapy (PR). DT is attractive but supposes long-term continuation, which we aimed to evaluate. Design and Methods Retrospective study, in a center prioritizing 2nd TSS, of 36 patients, including 19 with TSS failure and 17 with recurrence, out of 119 patients with CD treated by a first TSS, average follow-up 6.1 years (95% confidence interval 5.27-6.91). Control was defined as normalization of urinary free cortisol (UFC) and final treatment (FT) as the treatment allowing control at last follow-up. We also analyzed discontinuation rates of DT in published CD prospective clinical trials. Results Control was achieved in 33/36 patients (92%). DT was initiated in 29/36 patients (81%), allowing at least 1 normal UFC in 23/29 patients (79%) but was discontinued before last follow-up in 18/29 patients (62%). DT was FT in 11/29 patients (38%), all treated with cortisol synthesis inhibitors. Second TSS was FT in 8/16 (50%), BA in 14/14 (100%), and PR in 0/5. In published trials, discontinuation of DT was 11% to 51% at 1 year and 32% to 74% before 5 years. Conclusion DT allowed at least 1 normal UFC in 23/29 patients (79%) but obtained long-term control in only 11/29 (38%), as discontinuation rate was high, although similar to published data. Interestingly, a successful 2nd TSS was the cause for discontinuing efficient and well-tolerated DT in 5 patients. Further studies will show whether different strategies with cortisol synthesis inhibitors may allow for a lower discontinuation rate in patients not candidates for a 2nd TSS so that BA may be avoided in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC. Methods: Medical records of horses treated with weekly intramuscular injections of ERC (5  mg/mL, BOVA Aus) at either 0.01  mg/kg (high dose, HD) (n  =  10) or 0.005  mg/kg (low dose, LD) (n  =  30) were reviewed. Short-term ACTH responses were assessed at 5–8  days using a Wilcoxon signed ranked test. Longer-term ACTH responses (30 to 365  days) were assessed using generalised estimating equations. Results: Five to eight days after the first dose of LDERC, median adrenocorticotropic hormone (ACTH) concentration was lower (p  =  0.001), changing from 153  pg/mL (IQR: 78, 331) to 57  pg/mL (IQR: 30, 102). With HDERC, median ACTH concentration was also 153  pg/mL (IQR: 96, 185) before and then 56  pg/mL (IQR: 29, 86) after 5–8  days of treatment (p  =  0.047). Over 12  months of treatment, ACTH concentration ranged from 14 to >1,250  pg/mL (median: 51  pg/mL) in horses treated with LDERC and 20 to 472  pg/mL (median: 50  pg/ mL) in horses treated with HDERC. Measurements remained above the seasonal reference range in 39.3 and 52.3% of horses treated with LDERC and HDERC, respectively. Clinical improvement was reported by owners in 78.3 and 100% of horses treated with LDERC and HDERC, respectively. Partial, self-limiting inappetence was reported in 30.0% of LDERC and 60% HDERC cases. Seven horses exhibited lethargy (5 LDERC, 2 HDERC). Insulin concentrations measured 30  days post-ERC treatment were no different from baseline. Discussion: Clinical and endocrinological responses were consistent with results of previous reports of oral pergolide treatment. Weekly injection of ERC may be an effective alternative to pergolide; the 0.005  mg/kg dose appeared to be as effective, with less risk of inappetence, than the 0.01  mg/kg dose that has been reported previously [ABSTRACT FROM AUTHOR]

Background: Acute retinal pigment epitheliitis (ARPE) is a rare, idiopathic and self-limiting disease. The article aims to present ARPE in a patient using D2 dopamine receptor agonists for the treatment of hyperprolactinemia. Case presentation: A 28-year-old female during hyperprolactinaemia treatment suffered from a dyschromatopsia and a central visual field defect in the left eye. She noticed a deterioration of vision and discontinued the cabergoline administration. The woman had not been diagnosed with other chronic conditions and exhibited no symptoms of infection. Upon admission, the patient was subjected to a test for COVID-19, which was negative. The ophthalmological examination revealed a decrease in visual acuity to distance in the left eye, which amounted to 18/20 on the Snellen chart. A central scotoma was noted on the Amsler chart and a loss of pigment epithelium was visible on the fundus of the left eye. Fluorescein angiography showed a discrete window defect in the left one, with no signs of leakage. Optical coherence tomography (OCT) scans of the maculae revealed a characteristic change in the photoreceptor layer and retinal pigment epithelium (RPE) in the fovea in the left eye. The electrophysiological tests revealed decreased function of cells in macular region. A magnetic resonance imaging (MRI) of the head and orbits demonstrated an asymmetric pituitary gland without chiasm compression and discrete signal enhancement from the left optic nerve. The patient underwent observation during hospitalisation. She reported improved colour vision and a decreased scotoma in the centre of her visual field. In regular outpatient follow-ups, successive improvements in visual acuity, as well as a decreased RPE damage and outer photoreceptor layer loss during an OCT test were observed. Conclusions: A case of ARPE is reported in a patient taking medications for hyperprolactinemia. The role of dopamine receptor antagonists in the photoreceptor function and causation of ARPE needs further evaluation. [ABSTRACT FROM AUTHOR]

Endometrium scratching is a process of intentionally injuring the endometrium, and after scratching the endometrium, platelet-rich plasma (PRP) is inserted into the endometrial wall to improve pregnancy outcome. This case report revolves around a 33-year-old woman and her 38-year-old husband, who have been married for 3 years and were seeking treatment for their secondary infertility. The female had a history of hypothyroidism, and after the investigation, she was diagnosed with hyperprolactinemia. She also had a history of failure in vitro fertilization (IVF) cycles and two recurrent miscarriages upon investigation. The husband was found to have asthanozoospermia. After diagnosis of the female, we started treatment of cabergoline for hyperprolactinemia, a history of unsuccessful IVF cycles, and two recurrent miscarriages upon investigation. After the treatment of hyperprolactinemia in our clinic, we scheduled ovum pick-up and started the stimulation and performed intra-cytoplasmic sperm injection. After 1 month, we scheduled embryo transfer. On day 1, the progesterone scratched the endometrium wall and loaded the PRP to enhance the endometrial wall, and after an interval of 14 days, we checked the β-hCG level in the blood, and the result was positive, that is, the level was 1020 mIU/mL. The successful result of endometrial scratching with PRP improves pregnancy outcomes.

ABSTRACT: Prolactinoma is a benign tumor of the pituitary gland that leads to the overproduction of prolactin. It is the most common type of pituitary adenoma, accounting for approximately 50% of all pituitary tumors. The clinical presentation of prolactinoma varies depending on the level of prolactin elevation and the size of the tumor. In women, common symptoms include galactorrhea, amenorrhea, and infertility. Men may present with hypogonadism, decreased libido, erectile dysfunction, and gynecomastia. Large prolactinomas, known as macroadenomas, can cause mass effects such as headaches, visual disturbances due to compression of the optic chiasm, and hypopituitarism due to pressure on surrounding pituitary tissue. Understanding the pathogenesis of prolactinoma is crucial for developing effective treatments and improving patient outcomes. The development of prolactinomas involves a complex interplay of genetic, hormonal, and cellular factors. Treatment of prolactinoma aims to normalize prolactin levels, reduce tumor size, and alleviate symptoms. The first-line therapy is dopamine agonists, such as cabergoline and bromocriptine, with surgery and radiotherapy reserved for refractory cases. Furthermore, chemotherapeutic agent - temozolomide may be a treatment of choice in aggressive or malignant prolactinomas. By understanding the underlying mechanisms and different treatment methods, healthcare providers can optimize the management and outcomes for patients with prolactinoma.

ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (

This study prospective randomized controlled trial aims to test the impact of adding health education, awareness of some contributing factors and clinical guidance to therapeutic cabergoline given to infertile women with unexplained resistant hyperprolactinemia. It comprised 120 infertile women with unexplained persistent hyperprolactinemia not responding to therapeutic doses of cabergoline 1.5-2 mg/week who were subjected to proper history taking to exclude concomitant drug intake or possible brain problems in all cases. They were classified into group A (60 cases) who received health education and clinical guidance to search for possible contributing factors and were instructed to avoid them in addition to proper therapeutic doses of cabergoline, while group B (60 cases) received proper therapeutic doses of cabergoline only without clinical guidance. After 1 month, serum prolactin (PRL) was measured for all cases. All cases had high PRL level at the start of the study (79.9±28.4 [39-195] and 78.2±19.9 [42-189] in group A and B, respectively) without any significant difference. Pretreatment counselling revealed that lifestyle factors, sexual behaviors or feeding habits may contribute to resistant hyperprolactinemia in all cases without a significant difference between both groups. Serum PRL dropped significantly more in group A (20.14±10.31 [11-45] vs. 49.32±37.03 [12-100]) after combined health education, clinical guidance of the couple and proper treatment. It is concluded that lifestyle factors, sexual behaviors, and feeding habits would affect the response of hyperprolactinemia to treatment. Health education and clinical guidance with some advice to avoid them, would concomitantly improve the response of resistant hyperprolactinemia to therapeutic doses of dopamine agonists.

The priority treatment approach for prolactinomas is therapy with dopamine agonists, which allows for elimination of clinical symptoms, normalization of prolactin levels, reduction of the adenoma size and prevention of metabolic abnormalities in the majority of patients. Nevertheless, 10 to 20% of patients are resistant to dopamine agonists. The aim of this review is to analyze literature data on the source mechanisms and potential ways to overcome the resistance of prolactinomas to dopamine agonists. The criteria of a prolactinoma's resistance to dopamine agonists are as follows: 1) no normalization of serum prolactin levels and/or 2) no reduction of the adenoma volume by at least 50% after treatment of bromocriptine at a dose of ≤ 15 mg/day or cabergoline at a dose of ≤ 3 mg/week for at least 6 months. Full resistance is characterized by both no biochemical and no anti-tumor effects, whereas in partial resistance, prolactin levels can be decreased but not normalized, or the adenoma size can be reduced by less than 50% of the initial. The clinical and morphological predictors of prolactinoma resistance to dopamine agonists are male gender, young age, big size of the adenoma and its invasion into the sinus cavernosus, hypointensive and/or heterogeneous MRI signal on Т2 weighed images, and cystic components within the tumor. The main molecular genetic markers are: decreased expression of dopamine and estrogen receptors, higher proliferation index Ki-67 ≤ 3%, as well as the MENIN, AIP, SF3B1, PRDM2 gene mutations. In case of resistance to bromocriptine, it is recommended to switch the patient to cabergoline. In partial resistance to standard doses of cabergoline, it is possible to increase the dose up to a maximally tolerated. Neurosurgery and/or radiation surgery is recommended in cases of full resistance to dopamine agonists or an aggressive tumor. For very aggressive/malignant tumors, or in the event of their extended growth after surgery, temozolomide is recommended as adjuvant therapy.