Elevated Prolactin Levels Research Articles

Triphenyl phosphate-induced pericardial edema in zebrafish embryos is reversible following depuration in clean water

Triphenyl phosphate (TPHP) – a widely used organophosphate-based flame retardant – blocks cardiac looping during zebrafish development in a concentration-dependent manner, a phenotype that is dependent on disruption of embryonic osmoregulation and pericardial edema formation. However, it's currently unclear whether (1) TPHP-induced effects on osmoregulation are driven by direct TPHP-induced injury to the embryonic epidermis and (2) whether TPHP-induced pericardial edema is reversible or irreversible following cessation of exposure. Therefore, the objectives of this study were to determine whether TPHP-induced pericardial edema is reversible and whether TPHP causes injury to the embryonic epidermis by quantifying the number of DAPI-positive epidermal cells and analyzing the morphology of the yolk sac epithelium using scanning electron microscopy. First, we found that exposure to 5 μM TPHP from 24–72 h post-fertilization (hpf) did not increase prolactin – a hormone that regulates ions and water levels – in embryonic zebrafish, whereas high ionic strength exposure media was associated with elevated levels of prolactin. Second, we found that exposure to 5 μM TPHP from 24–72 hpf did not decrease DAPI-positive epidermal cells within the embryonic epithelium, and that co-exposure with 2.14 μM fenretinide – a synthetic retinoid that promotes epithelial wound repair – from 24–72 hpf did not mitigate the prevalence of TPHP-induced epidermal folds within the yolk sac epithelium when embryos were exposed within high ionic strength exposure media. Finally, we found that the pericardial area and body length of embryos exposed to 5 μM TPHP from 24–72 hpf were similar to vehicle-treated embryos at 120 hpf following transfer to clean water and depuration of TPHP from 72–120 hpf. Overall, our findings suggest that (1) the ionic strength of exposure media may influence the baseline physiology of zebrafish embryos; (2) TPHP does not cause direct injury to the embryonic epidermis; and (3) TPHP-induced effects on pericardial area and body length are reversible 48 h after transferring embryos to clean water.

The relationship between metabolic stress and Anti- Müllerian hormone (AMH) in women hospitalized in intensive care units

Objective: Our study aimed to investigate the levels of anti-Müllerian hormone (AMH) to determine ovarian reserve in women in intensive care units experiencing metabolic and physiological stress. Materials and Methods: For this purpose, 37 women were hospitalized in the intensive care unit (ICU) of Siirt Training and Research Hospital between November 2022 and February 2023. The same number of healthy control groups were included in the study. Patient selection was based on acute physiology and chronic health assessment (APACHI II) score and injury severity score (ISS).Anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) thyroid stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH), cortisol. , prolactin, C-reactive hormone (CRP) serum levels were examined Results: There was no significant difference in mean age between intensive care patients (29.3±8.3 , n=37) and control group (28.0±0.0, n=37) (p=0.349). A statistically significant difference was found between the AMH values between the patients hospitalized in the intensive care unit and the control group (p=0.012).AMH values were significantly lower in ICU patients. However, the T3 value was observed to be significantly lower in ICU patients compared to the control group (p < 0.0001). Additionally, prolactin, CRP, and cortisol values were found to be statistically significantly higher. Conclusion: This study revealed a significant decrease in anti-Müllerian hormone (AMH) levels among women experiencing metabolic and physiological stress in intensive care units. The lowered AMH levels suggest a potential impact on ovarian reserve in such conditions. Additionally, the observation of reduced T3 levels in ICU patients could indicate thyroid function alterations during times of stress. The elevated prolactin, CRP, and cortisol levels further underscore the physiological disruptions experienced by ICU patients. These findings emphasize the importance of considering hormonal and metabolic changes in critically ill women, particularly in relation to their ovarian health. Further research is warranted to elucidate the intricate mechanisms underlying these hormonal alterations and their potential long-term implications.

Impaired Prolactin-Lowering Effects of Metformin in Women with Polycystic Ovary Syndrome.

The effect of metformin on prolactin concentration seems to be sex-dependent. The aim of this study was to determine whether the androgen status modulates the impact of metformin on plasma prolactin levels in women. This study included two matched groups of prediabetic women with hyperprolactinemia: 25 with PCOS and 25 control subjects with androgen levels within the reference range and with normal ovarian morphology. Glucose homeostasis markers, prolactin, the remaining anterior pituitary hormones, sex hormones, SHBG and IGF-1 were determined before and after six months of metformin treatment. At baseline, both groups differed in LH, LH/FSH ratio, testosterone, FAI, DHEA-S, androstenedione and estradiol. Although metformin improved insulin sensitivity and increased SHBG in both study groups, these effects were more pronounced in control subjects than in women with PCOS. In control subjects, the drug decreased total and monomeric prolactin and increased LH. In women with PCOS, metformin reduced LH, LH/FSH ratio, testosterone and FAI. In the control group, the impact on total and monomeric prolactin positively correlated with their baseline levels and with the degree of improvement in insulin sensitivity, as well as negatively correlated with testosterone and FAI. In women with PCOS, treatment-induced changes in testosterone and FAI positively correlated with the changes in LH and LH/FSH ratio. The obtained results suggest that the prolactin-lowering properties of metformin are less pronounced in women with coexisting PCOS than in women with elevated prolactin levels, probably owing to the increased production of endogenous testosterone.

The role of prolactin in the suppression of the response to restraint stress in the lactating mouse.

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a well-characterised maternal adaptation that limits the exposure of the offspring to maternally-derived stress hormones. This current study has investigated the possible involvement of the lactogenic hormone, prolactin, in this physiologically important adaptation. As expected, circulating prolactin levels were higher in unstressed lactating mice compared to their virgin counterparts. Interestingly however, the ability of an acute period of restraint stress to further elevate prolactin levels was diminished in the former group. The stress-induced rise in prolactin levels in the virgin animals was concurrent with an increase in prolactin receptor activation within the adrenal cortical cells. This adrenal response was not seen in either the stressed or control lactation group, an observation that may be in part explained by the observed downregulation of prolactin receptor mRNA expression within this tissue. Further evidence of suppression of the HPA axis during lactation was revealed using in situ hybridisation to demonstrate that while acute restraint stress increased corticotrophin releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus in both virgin and lactating mice, the magnitude of this response was reduced in the latter group. This potentially adaptive response did not, however, appear to result from the altered prolactin profile during lactation because it was not affected by the pharmacological suppression of prolactin secretion from the pituitary. This study therefore suggests that during lactation the response of the HPA axis to stress is suppressed at multiple physiological levels which are mediated by both prolactin-dependent and prolactin-independent mechanisms.

Verification of Roche reference ranges for serum prolactin in children, adolescents, adults, and the elderly

Reference intervals (RIs) for prolactin are of high clinical importance for diagnosis, treatment, and prognosis of hypothalamic-pituitary disorders. The aim of this study was to verify the Roche reference ranges for serum prolactin in children, adolescents, adults, and the elderly. : An indirect method based on currently laboratory data was used on the reference ranges. Nine thousand one hundred and thirteen prolactin results were included. Pregnancy, lactation, exercise and reported pathologies were ruled out and only samples were collected between 8AM and 12PM were used. Reference ranges with a confidence interval of 95% (95% CI) were estimated. : Compared to the manufacturer's reference values and for the corresponding age group, the median values obtained in our study were 10 – 60% higher depending on the age and sex of the patients. Elevated levels of serum prolactin were observed in the neonatal period and values decrease until median values near 200 mUI/L in childhood. During the children's period, no gender differences were observed for prolactin level. The gender difference in prolactin levels became significant from pre-adolescence until the age of 60. Prolactin levels increased significantly (p<0.001) between children and young adults, followed by a gradual and continuous decrease until young senior age.: The prolactin reference values proposed by the manufacturer in the data sheet appeared unsuitable. Laboratories should review reference ranges, and a partitioning with sex and different age groups may be appropriate.

Hyperprolactinemia and male sexual function: focus on erectile dysfunction and sexual desire.

The present paper aims to analyze and discuss the available evidence supporting the relationship between male sexual function and elevated prolactin (PRL) levels (HPRL). Two different sources of data were analyzed. Clinical data were derived from a series of patients seeking medical care for sexual dysfunction at our Unit. Out of 418 studies, 25 papers were used with a meta-analytic approach to evaluate the overall prevalence of HPRL in patients with erectile dysfunction (ED) and to study the influence of HPRL and its treatment on male sexual function. Among 4215 patients (mean age 51.6 ± 13.1 years) consulting for sexual dysfunction at our Unit, 176 (4.2%) showed PRL levels above the normal range. Meta-analytic data showed that HPRL is a rare condition among patients with ED (2 [1;3]%). Either clinical and meta-analytic data confirm a stepwise negative influence of PRL on male sexual desire (S = 0.00004 [0.00003; 0.00006]; I = -0.58915 [-0.78438; -0.39392]; both p < 0.0001 from meta-regression analysis). Normalization of PRL levels is able to improve libido. The role of HPRL in ED remains inconclusive. Data from a meta-analytic approach showed that either HPRL or reduced T levels were independently associated with ED rates. The normalization of PRL levels only partially restored ED. HPRL did not significantly contribute to ED severity, in our clinical setting. In conclusion, treating HPRL can restore normal sexual desire, whereas its effect on erection is limited.

The Effect of Metformin on Plasma Prolactin Levels in Young Women with Autoimmune Thyroiditis.

Metformin decreases elevated prolactin levels, which are frequently found in patients with thyroid disorders. The aim of this study was to investigate whether thyroid autoimmunity modulates the impact of metformin on lactotrope secretory function. This study compared two matched groups of young women with prediabetes and mild-to-moderate prolactin excess: 28 subjects with coexisting euthyroid autoimmune thyroiditis (group 1) and 28 individuals without thyroid disorders (group 2), treated for six months with metformin (3 g daily). Thyroid antibody titers, glucose homeostasis markers, prolactin, thyrotropin, free thyroid hormones, FSH, LH, ACTH, IGF-1 and hsCRP were assessed at the beginning and at the end of the study. At entry, the study groups differed in antibody titers and hsCRP levels. Although the improvement in glucose homeostasis and the decrease in hsCRP levels were observed in both study groups, they were more pronounced in group 2. Only in group 2 did metformin reduce circulating prolactin levels (both total and monomeric). Prolactin-lowering properties of metformin positively correlated with baseline prolactin levels, baseline antibody titers (in group 1) and with the degree of reduction in hsCRP levels. The obtained results suggest that autoimmune thyroiditis may attenuate the impact of metformin on lactotrope secretory function.

Macroprolactinemia: a mini-review and update on clinical practice

Hyperprolactinemia is common among infertile patients, with up to 15%-20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%-10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%-46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL.

Reproductive Function during Lactation

The phenomenon of locational amenorrhea, in which postpartum women experience temporary suppression of menstruation and fertility during breastfeeding, has long been recognized. This natural contraceptive effect is primarily attributed to elevated prolactin levels, which are stimulated by frequent suckling and inhibit the release of gonadotropinreleasing hormones and, subsequently, the menstrual cycle. However, the extent of lactational amenorrhea contraceptive efficacy varies among individuals owing to factors such as breastfeeding patterns, infant feeding behavior, and maternal health. Recent research has shed light on the underlying mechanisms governing the interplay between lactation and reproductive functions. Studies have shown that, while exclusively on-demand breastfeeding offers a higher level of contraceptive protection, introducing supplementary foods and reducing breastfeeding frequency can shorten the duration of lactational amenorrhea, potentially leading to earlier ovulation and conception. Additionally, the hormonal milieu during lactation may not be entirely suppressive, because occasional instances of follicular development and ovulation have been reported before the return of regular menstruation. Understanding the intricacies of reproductive function during lactation is important not only for family planning but also for optimizing maternal and infant health. The duration of exclusive breastfeeding has been associated with various health benefits for both the mother and the child, including enhanced immune protection, cognitive development, and a reduced risk of certain chronic diseases. Lactational amenorrhea serves as a physiological contraceptive method, but its efficacy is influenced by individual variations and breastfeeding practices. Further research is needed to elucidate the complex hormonal interactions and refine guidelines for optimal family planning during the postpartum period. Balancing the benefits of extended breastfeeding with a desire for family planning requires a comprehensive understanding of the intricate relationship between lactation and reproductive physiology

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study.

Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline's cardiometabolic effects.

A giant invasive macroprolactinoma with recurrent nasal bleeding as the first clinical presentation: case report and review of literature

BackgroundGiant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma.We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom.Case presentationA 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced.ConclusionThis case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.

Abstract #1413579: Rathke Cleft Cyst Unveiling Incidental Prolactin Producing Adenoma

Rathke cleft cysts (RCCs) are benign sellar and or/suprasellar lesions that arise from remnants of Rathke's pouch. Pituitary hormonal dysfunction associated with RCCs most often present as hormonal deficiencies due to compression. However pituitary hyper-secretion may coexist with RCC challenging diagnosis and management. A 37-year-old female presented with worsening headache, bilateral blurry vision and pressure-like eye pain for two weeks. She denied any galactorrhea or irregular periods. Her medications included as-needed butalbital-acetaminophen-caffeine and alprazolam. CT Head without IV contrast revealed a pituitary lesion measuring 1.9 cm extending near the inferior margin of the optic chiasm. Subsequent MRI Pituitary with and without IV contrast revealed an enhancing sellar/suprasellar solid lesion measuring 1.6 x 2.7 x 1.9 cm with small hypoenhancing components associated with expansion of the sella, rightward infundibulum deviation, mass effect on the optic chiasm and left cavernous sinus invasion. Pituitary secretion workup revealed an elevated serum prolactin level of 50.4 ng/mL (range 4.8 - 23.3 ng/mL). Repeat prolactin level was 75.7 mg/ml. Dilution studies 1:10 and 1:100 revealed prolactin levels of 78.3 ng/mL and 75.9 ng/mL respectively; absence of hook effect. Her elevated prolactin was attributed to stalk effect given the large size of her sellar mass and relatively minimally elevated prolactin level. Serum Alpha Subunit, ILGF-1, TSH, FT4, LF, FSH, AM cortisol and ACTH level were all normal. She underwent endoscopic transsphenoidal pituitary mass resection with pathology results revealing prolactin producing adenoma and RCC. Immunostains were strongly positive for chromogranin A and prolactin while negative for FSH, ACTH, TSH, beta hCG, GH. Prolactin levels 11 days post-resection remained elevated at 50.7 ng/mL. She continued to have regular periods without galactorrhea. Additionally, she expressed desire to attain pregnancy. This case illustrates the presence of a secreting pituitary prolactinoma in the setting of an RCC. Whether these two entities share a common pathophysiology or simply co-exist is unknown. In one study of 33 surgically treated RCC at presentation, 60% had gonadotroph deficiency, 36% had ACTH deficiency, 36% had TSH deficiency, 18% had ADH deficiency and 31% had hyperprolactinemia (1). It is possible that the majority of this patient 's sellar mass was comprised of RCC as a much higher prolactin level would have been expect for the size of her mass. Interesting, her sellar mass exhibited enhancement which is uncharacteristic for RCC, classical described as cystic lesions without calcification or enhancement. Given that her post-resection prolactin level remained elevated and she desires pregnancy, she may require dopamine agonist therapy.

Abstract #1398813: A Rare Case of Acromegaly with Negative Immunohistochemical Staining for Growth Hormone

We are presenting a case of mixed prolactin and growth hormone (GH)-pituitary tumor with negative immunostaining for GH. 81-year-old male with history of type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and colon polyps was found to have a pituitary macroadenoma during evaluation of his visual disturbances. Years before the presentation, he noticed his shoe size had increased and his wife observed his jaw becoming more prominent. Physical exam was notable for enlarged nose, mandibular prognathism, and enlarged hands. Pre-operative laboratory results were remarkable for significantly elevated levels of insulin-like growth factor-1 (IGF-1), GH, and prolactin. He underwent transsphenoidal resection (TSPR) of the mass and pathology demonstrated a lactotroph adenoma, negative for GH immunostaining. After surgery he was started on cabergoline 0.5mg PO twice weekly. Three months afterwards his IGF-1 level remained elevated at 415 ng/mL. Acromegaly was confirmed by an elevated GH level of 13.8 ng/mL 2-hours after oral glucose challenge, then a long-acting somatostatin analogue depot was initiated for treatment. In the first year of therapy, he had weight loss and hypoglycemia that required discontinuation of insulin therapy. His IGF-1 and GH levels decreased to within age-appropriate ranges. His prolactin level returned to normal and cabergoline was stopped after a successful discontinuation trial. Clinical suspicion for acromegaly is confirmed by elevated IGF-1 and GH levels. When a GH-secreting pituitary adenoma is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is not common for these tumors to stain negative for GH in the presence of clinical and biochemical acromegaly. The opposite—termed silent somatotroph— is more common and may represent an early stage in the development of a somatotroph adenoma. Failure to provide adequate diagnostic tissue, histopathology misread, or loss of antigenicity during fixation or embedding may be reasons for false negatives. However, it has been suggested that sparse cytoplasmic stores of GH do not parallel the hypersecretion of GH and may reduce staining capacity. Thus, a diagnosis of acromegaly should be made in patients with clinical and biochemical findings, even in the absence of GH immunostaining.

The Combination of Dopamine Agonist Treatment and Surgery May Be the Best Option in Challenging Prolactinoma Cases: A Single-Centre Experience

To investigate the initial and long-term remission rates, factors related to remission, secondary treatments, and outcomes for patients with prolactinoma who underwent endoscopic transsphenoidal surgery (ETSS). The medical files of the 45 prolactinoma patients who underwent ETSS between 2015 and 2022 were retrospectively reviewed. Relevant demographic and clinical data were obtained. Twenty-one (46.7%) patients were female. The median age of patients at ETSS was 35 (interquartile range, 22.5-50) years. The median clinical follow-up of patients was 28 (interquartile range 12-44) months. The initial surgical remission rate was 60%. Recurrence was detected in 7 patients (25.9%). Postoperative dopamine agonists were used in 25 patients, radiosurgery in 2, and second ETSS in 4 patients. After these secondary treatments, the long-term biochemical remission rate was 91.1%. The factors associated with failure in surgical remission are: male gender, older age, higher tumor size, advanced Knosp and Hardy stage, and elevated prolactin level at diagnosis. A prolactin level of <19ng/mL in the first postoperative week predicted surgical remission with a sensitivity of 77.8% and a specificity of 70.6% in patients who received preoperative dopamine agonist treatment. In macro adenomas and/or giant adenomas with cavernous sinus invasion, and significant suprasellar extension, which constitutes the difficult part of prolactinoma treatment, neither surgery nor medical treatment alone may be effective enough. Both treatment modalities should be carried out together by a team of neurosurgery and endocrinology in the management of these patients.

Ayurveda management of primary infertility associated with hypothyroidism and hyperprolactinemia: A case report

Abstract: Hypothyroidism and hyperprolactinemia adversely affect the fertility potential of women by impairing ovulatory function. There is a high prevalence of hypothyroid-associated hyperprolactinemia in infertility. Long-standing hypothyroidism promotes hyperprolactinemia which leads to irregular periods, and anovulation and ultimately results in infertility. This is a case report of the primary infertility of a couple married for seven years. The female partner had anovulatory cycles with elevated levels of Thyroid-Stimulating Hormone (TSH) and prolactin. Ayurveda treatment was planned in this case to evaluate its role to address hormonal imbalance, ensuring regular ovulation, and thereby helping to have a normal pregnancy. Based on the parameters of Ayurvedic Science, this case was diagnosed as Vandhyatva (~infertility), which was treated with both internal medicines and external therapies including Shodhana (~bio cleansing therapy) and Shamana chikitsa (~therapy which is aimed at mitigating the disease by pacifying Dosha). After the treatment, TSH was reduced from 14.99 to 4.0 μIU/mL and the prolactin level was reduced from 47.23 to 13 ng/mL. The intervention resulted in conception within three months, and she delivered a full-term female baby.

Antipsychotic-Related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth: A 3-Month Cohort Study

Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce. Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for≥4 weeks were followed for≤12 weeks on clinician's-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale-based SeAEs were assessed monthly. Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants= 55.1%, mood spectrum disorders= 56.3%, schizophrenia spectrum disorders= 24.0%, aggressive-behavior disorders= 19.7%; SDA-naive= 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median= 56.1 ng/mL/incidence= 93.5%/44.5%), followed by olanzapine (median= 31.4 ng/mL/incidence= 42.7/76.4%/7.3%), quetiapine (median= 19.5 ng/mL/incidence= 39.7%/2.5%) and aripiprazole (median= 7.1 ng/mL/incidence= 5.8%/0.0%) (all p< .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had≥1 newly incident SeAEs (risperidone= 29.4%, quetiapine= 29.0%, olanzapine= 25.5%, aripiprazole= 22.1%, p= .59). The most common SeAEs were menstrual disturbance= 28.0% (risperidone= 35.4%, olanzapine= 26.7%, quetiapine= 24.4% aripiprazole= 23.9%, p= .58), decreased erections= 14.8% (olanzapine= 18.5%, risperidone= 16.1%, quetiapine= 13.6%, aripiprazole= 10.8%, p= .91) and decreased libido= 8.6% (risperidone= 12.5%, olanzapine= 11.9%, quetiapine= 7.9%, aripiprazole= 2.4%, p= .082), with the least frequent being gynecomastia= 7.8% (quetiapine= 9.7%, risperidone= 9.2%, aripiprazole= 7.8%, olanzapine= 2.6%, p= 0.61), galactorrhea= 6.7% (risperidone= 18.8%, quetiapine= 2.4%, olanzapine= 0.0%, aripiprazole= 0.0%, p= .0008), and mastalgia= 5.8% (olanzapine= 7.3%, risperidone= 6.4%, aripiprazole= 5.7%, quetiapine= 3.9%, p= .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p= .013) and erectile dysfunction (p= .037) at week 4, and with galactorrhea at week 4 (p= .0040), week 12 (p= .013), and last visit (p< .001). Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.

Screening for possible hypopituitarism following mild traumatic brain injury: The first all-female study. Who do we need to evaluate further?

Studies on hypopituitarism (HP) following mild traumatic brain injury (mTBI) have focused on male populations although women may be more susceptible to the sequelae of mTBI. This is, to the best of our knowledge, the first all-female study screening for HP following mTBI. Screening for possible HP in female athletes reporting a history of one or more mTBI. Pituitary hormone screening blood tests (SBT) were performed in 133 of the 151 female athletes included. Repeated results outside the reference value (O-RV) were considered abnormal necessitating further endocrinological evaluation. Repeated SBT were O-RV in 88 women (66.2%). Decreased levels of serum insulin growth factor 1 (S-IGF1) were found in 55.6% of participants and elevated levels of serum prolactin (S-prolactin) in 22.6%. Serum cortisol levels were below the RV in 6.0% and thyroid hormonal levels in 11.3%. Lower age and increased number of mTBI symptoms correlated significantly with the risk of hormonal results O-RV. The majority of the study population had SBT O-RV, warranting further workup of possible HP. Decreased levels of S-IGF1 were most commonly observed followed by elevated S-prolactin possibly indicating hypothalamic-pituitary impairment. Lower age and increased number of symptoms of mTBI may indicate the need to screen for HP.

Clinical Presentations of Drug-Induced Hyperprolactinaemia: A Literature Review.

Screening for drug-induced hyperprolactinaemia, a condition characterised by higher-than-normal levels of serum prolactin induced by drug treatments, requires a comprehensive understanding of the clinical presentations and long-term complications of the condition. Using two databases, Embase and MEDLINE, we summarised the available evidence on the clinical presentations and long-term complications of drug-induced hyperprolactinaemia. Clinical and observational studies reporting on drug treatments known or suspected to induce hyperprolactinaemia were included. Database searches were limited to the English language; no date or geographic restrictions were applied. Fifty studies were identified for inclusion, comprising a variety of study designs and patient populations. Most data were reported in patients treated with antipsychotics, but symptoms were also described among patients receiving other drugs, such as prokinetic drugs and antidepressants. Notably, the diagnosis of drug-induced hyperprolactinaemia varied across studies since a standard definition of elevated prolactin levels was not consistently applied. Frequent clinical presentations of hyperprolactinaemia were menstrual cycle bleeding, breast or lactation disorders, and sexual dysfunctions, described in 80% (40/50), 74% (37/50), and 42% (21/50) of the included studies, respectively. In the few studies reporting such symptoms, the prevalence of vaginal dryness impacted up to 53% of females, and infertility in both sexes ranged from 15 to 31%. Clinicians should be aware of these symptoms related to drug-induced hyperprolactinaemia when treating patients with drugs that can alter prolactin levels. Future research should explore the long-term complications of drug-induced hyperprolactinaemia and apply accepted thresholds of elevated prolactin levels (i.e., 20ng/mL for males and 25ng/mL for females) to diagnose hyperprolactinaemia as a drug-induced adverse event.Trial Registration PROSPERO International Prospective Register Of Systematic Reviews (CRD42021245259).

The Involvement of Prolactin in Stress-Related Disorders.

The most important and widely studied role of prolactin (PRL) is its modulation of stress responses during pregnancy and lactation. PRL acts as a neuropeptide to support physiological reproductive responses. The effects of PRL on the nervous system contribute to a wide range of changes in the female brain during pregnancy and the inhibition of the hypothalamic-pituitary axis. All these changes contribute to the behavioral and physiological adaptations of a young mother to enable reproductive success. PRL-driven brain adaptations are also crucial for regulating maternal emotionality and well-being. Hyperprolactinemia (elevated PRL levels) is a natural and beneficial phenomenon during pregnancy and lactation. However, in other situations, it is often associated with serious endocrine disorders, such as ovulation suppression, which results in a lack of offspring. This introductory example shows how complex this hormone is. In this review, we focus on the different roles of PRL in the body and emphasize the results obtained from animal models of neuropsychiatric disorders.

Hyperprolactinaemia is common in Chinese premenopausal women with breast diseases.

Purpose: Hyperprolactinaemia has been proposed to play a role in breast lesions pathophysiology. Thus far, controversial results have been reported for the relationship between hyperprolactinaemia and breast lesions. Moreover, the prevalence of hyperprolactinaemia in a population with breast lesions is scarcely reported. We aimed to investigate the prevalence of hyperprolactinaemia in Chinese premenopausal women with breast diseases, and explore the associations between hyperprolactinaemia with different clinical characteristics. Methods: This was a retrospective cross-sectional study performed in the department of breast surgery of Qilu hospital of Shandong University. Overall, 1,461 female patients who underwent the serum prolactin (PRL) level assay before breast surgery from January 2019 to December 2020 were included. Patients were divided into two groups: before and after menopause. Data were analyzed using SPSS 18.0 software. Results: The results showed an elevated PRL level in 376 of the 1,461 female patients with breast lesions (25.74%). Furthermore, the proportion of hyperprolactinemia among premenopausal patients with breast disease (35.75%, 340/951) was significantly higher than among postmenopausal patients with breast disease (7.06%, 36/510). In premenopausal patients, the proportion of patients with hyperprolactinaemia and the mean serum PRL level were significantly higher in those diagnosed with fibroepithelial tumours (FETs) and in younger patients (aged < 35years) than in those with non-neoplastic lesions and in those aged ≥ 35years (both p < 0.05). Especially, the prolactin level exhibited steady ascending tendency for positive correlation with FET. Conclusion: Hyperprolactinaemia is prevalent in Chinese premenopausal patients with breast diseases, especially in those with FETs, which implies a potential association, to some extent, between the PRL levels in various breast diseases.