Effects Of Growth Hormone Replacement Therapy Research Articles

Managing Estrogen Therapy in the Pituitary Patient

Growth hormone (GH) regulates metabolic and physical health in the adult human. Because the GH system is regulated by estrogens, therapeutic estrogen compounds are likely to affect metabolic health. Estrogens are available for oral and parenteral use in natural, prodrug, and synthetic formulations including selective estrogen receptor modulators (SERMs). This review covers the pharmacology of estrogen and the effects on GH action to inform judicious use in the pituitary patient. The effects on the GH system are route dependent due to first-pass hepatic metabolism. Oral but not parenteral estrogen compounds inhibit GH action, reducing hepatic insulin-like growth factor-1 (IGF-1) production, protein anabolism, and fat utilization. In patients with GH deficiency, oral estrogen therapy exacerbates the degree of hyposomatotrophism and attenuates the beneficial effects of GH replacement therapy, effects that are greater with contraceptive than replacement doses. Surveys report that less than one-fifth of hypopituitary women are appropriately replaced by a transdermal route and up to half on oral therapy are inappropriately treated with contraceptive steroids. In acromegaly, however, estrogens, especially synthetic formulations of greater potency, reduce IGF-1, improving disease control, an effect also observed in men treated with SERMs. The route-dependent effects and potency of estrogen formulations are important considerations for optimizing the management of hypogonadal patients with pituitary disease, in particular GH deficiency and acromegaly. For hypopituitary women, estrogens should be replaced by a nonoral route. For acromegaly, oral estrogen formulations can be considered as simple adjuvant therapy for disease control.

MRI Assessment of Cardiac Function and Morphology in Adult Patients With Growth Hormone Deficiency: A Systematic Review and Meta-Analysis.

BackgroundAdult GH deficiency (GHD) has been described as a heterogeneous condition characterized by many clinical modifications, such as metabolic alterations, impaired quality of life, and increased mortality. The clinical relevance of cardiac involvement remains, however, only partially elucidated.MethodsPubMed/Medline, EMBASE, Cochrane library, OVID and CINAHL databases were systematically searched until February 2022 for studies evaluating cardiac function and morphology by magnetic resonance imaging in adult patients with GHD. Effect sizes were pooled through a random-effect model.ResultsFour studies were considered in the meta-analysis. With respect to the left ventricle, GHD patients were characterized by a lower stroke-volume-index (-3.6 ml/m2, standardized mean difference (SMD) -0.60, 95%CI [-1.15,-0.05], p=0.03), lower end-diastolic-volume-index (-6.2 ml/m2, SMD -0.54, 95%CI [-0.97,-0.10], p=0.02) and, after accounting for possible biases, lower mass-index (-15.0 g/m2, SMD -1.03, 95%CI [-1.89,-0.16], p=0.02). With respect to the right ventricle, a lower end-diastolic-volume-index (-16.6 ml/m2, SMD -1.04, 95%CI [-2.04,-0.03], p=0.04) and a borderline-significant lower stroke-volume-index (-5.0 ml/m2, SMD -0.84, 95%CI [-1.77,0.08], p=0.07) could be observed. Data about the effect of GH replacement therapy highlighted a significant increase in left ventricular mass-index after treatment initiation (+3.7 g/m2, 95%CI [1.6,5.7], p<0.01).ConclusionWith respect to the left ventricle, our results confirmed those retrieved by echocardiographic studies. In addition, significant alterations were demonstrated also for the right ventricle, for which echocardiographic data are nearly absent. This supports the thesis of a biventricular cardiac involvement in patients with GHD, with a similar pattern of morphological and functional alterations in both ventricles.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Traumatic Brain Injury as Frequent Cause of Hypopituitarism and Growth Hormone Deficiency: Epidemiology, Diagnosis, and Treatment.

Traumatic brain injury (TBI)-related hypopituitarism has been recognized as a clinical entity for more than a century, with the first case being reported in 1918. However, during the 20th century hypopituitarism was considered only a rare sequela of TBI. Since 2000 several studies strongly suggest that TBI-mediated pituitary hormones deficiency may be more frequent than previously thought. Growth hormone deficiency (GHD) is the most common abnormality, followed by hypogonadism, hypothyroidism, hypocortisolism, and diabetes insipidus. The pathophysiological mechanisms underlying pituitary damage in TBI patients include a primary injury that may lead to the direct trauma of the hypothalamus or pituitary gland; on the other hand, secondary injuries are mainly related to an interplay of a complex and ongoing cascade of specific molecular/biochemical events. The available data describe the importance of GHD after TBI and its influence in promoting neurocognitive and behavioral deficits. The poor outcomes that are seen with long standing GHD in post TBI patients could be improved by GH treatment, but to date literature data on the possible beneficial effects of GH replacement therapy in post-TBI GHD patients are currently scarce and fragmented. More studies are needed to further characterize this clinical syndrome with the purpose of establishing appropriate standards of care. The purpose of this review is to summarize the current state of knowledge about post-traumatic GH deficiency.

Effects of growth hormone-replacement therapy in patients with Prader-Willi syndrome - review of recent clinical trials

Introduction and objective: Prader-Willi syndrome (PWS) is a severe genetic disorder being manifested by several symptoms such as infantile hypotonia and poor thriving outcomes, low height, hyperphagia, endocrine, reproductive and internal malfunctions and malformations. In the disease treatment, growth hormone (GH)-replacement therapy is commonly carried on. In this article, we sum up the latest clinical trials’ results concerning the effectiveness and safety of GH-replacement therapy.Abbreviated description of the state of knowledge: Taking into consideration six clinical trials performed in the years 2019-2020, most of them showed positive results of GH-replacement therapy in PWS patients, not only in case of better motor skills or body composition, but also concerning their social and adaptive functioning. Moreover, as for the cessation of GH treatment, some authors seem to highlight no deterioration in cognitive functioning in patients who attained adult height after GH-treatment.Summary: GH-replacement therapy seems to be a good therapeutic option for PWS-affected individuals. Nonetheless, in our research we did not come across on any clinical trials with more than one-year-long observations. Thus, on the long term, these results can not exclude a gradual deterioration of cognitive functioning.

Long-term effects of GH replacement therapy on thyroid function in children with GH deficiency

Long-term effects of GH replacement therapy on thyroid function in children with GH deficiency

Treatment with Growth Hormone for Adults with Growth Hormone Deficiency Syndrome: Benefits and Risks.

Pharmacological treatment of growth hormone deficiency (GHD) in adults began in clinical practice more than 20 years ago. Since then, a great volume of experience has been accumulated on its effects on the symptoms and biochemical alterations that characterize this hormonal deficiency. The effects on body composition, muscle mass and strength, exercise capacity, glucose and lipid profile, bone metabolism, and quality of life have been fully demonstrated. The advance of knowledge has also taken place in the biological and molecular aspects of the action of this hormone in patients who have completed longitudinal growth. In recent years, several epidemiological studies have reported interesting information about the long-term effects of GH replacement therapy in regard to the possible induction of neoplasms and the potential development of diabetes. In addition, GH hormone receptor polymorphism could potentially influence GH therapy. Long-acting GH are under development to create a more convenient GH dosing profile, while retaining the excellent safety, efficacy, and tolerability of daily GH. In this article we compile the most recent data of GH replacement therapy in adults, as well as the molecular aspects that may condition a different sensitivity to this treatment.

Physiologic Growth Hormone-Replacement Therapy and Craniopharyngioma Recurrence in Pediatric Patients: A Meta-Analysis.

A systematic review and meta-analysis were conducted to examine the effect of growth hormone-replacement therapy (GHRT) on the recurrence of craniopharyngioma in children. PubMed, Embase, and Cochrane databases were searched through April 2017 for studies that evaluated the effect of GHRT on the recurrence of pediatric craniopharyngioma. Pooled effect estimates were calculated with fixed- and random-effects models. Ten studies (n= 3487 patients) metall inclusion criteria, including 2 retrospective cohorts and 8 case series. Overall, 3436 pediatric patients were treated with GHRT after surgery and 51 were not. Using the fixed effect model, we found that the overall craniopharyngioma recurrence rate was lower among children who were treated by GHRT (10.9%; 95% confidence interval 9.80%-12.1%; I2= 89.1%; P for heterogeneity <0.01; n= 10 groups) compared with those who were not (35.2%; 95% confidence interval 23.1%-49.6%; I2= 61.7%; P for heterogeneity= 0.11; n= 3); the P value comparing the 2 groups was <0.01. Among patients who were treated with GHRT, subgroup analysis revealed that there was a greater prevalence of craniopharyngioma recurrence among studies conducted outside the United States (P < 0.01), single-center studies (P < 0.01), lower impact factor studies (P= 0.03), or studies with a lower quality rating (P= 0.01). Using the random-effects model, we found that the results were not materially different except for when stratifying by GHRT, impact factor, or study quality; this led to nonsignificant differences. Both Begg's rank correlation test (P= 0.7) and Egger's linear regression test (P= 0.06) indicated no publication bias. This meta-analysis demonstrated a lower recurrence rate of craniopharyngioma among children treated with GHRT than those who were not.

Long-term effects of growth hormone (GH) replacement therapy on hematopoiesis in a large cohort of children with GH deficiency.

The aim of our prospective case-control study was to evaluate long-term effects of GH replacement therapy on erythrocytes parameters, leukocytes, and platelets numbers in a large cohort of children with isolated GH deficiency (GHD). Hemoglobin (Hb) concentration, hematocrit (Hct), mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, number of erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes and platelets, ferritin, and C-reactive protein were evaluated in 85 children with isolated GHD (10.20±3.50years) before and annually during the first 5years of GH replacement therapy and in 85 healthy children age and sex comparable to patients during 5years of follow-up. Compared with controls, GHD children at study entry showed lower Hb (-1.18±0.87 vs. -0.40±0.90 SDS, p<0.0001), red cells number (-0.24±0.81 vs. 0.25±1.14 SDS, p<0.0001), and Hct (-1.18±0.86 vs. -0.68±0.99 SDS, p<0.0001). Twelve GHD patients (14%) showed a normocytic anemia. GH therapy was associated with a significant increase in Hb, Hct, and red cells number which became all comparable to controls within the first 2years of treatment. Moreover, hemoglobin levels normalized in all anemic GHD patients after 5years of therapy. No difference between patients and controls was found in leukocytes and platelets numbers neither at baseline nor during the study. GHD in childhood is associated with an impairment of erythropoiesis which causes a normocytic anemia in a considerable percentage of patients. GH replacement therapy exerts a beneficial effect leading to a significant increase of erythrocytes parameters and recovery from anemia. Neither GHD nor GH replacement treatment exerts effects on leukocytes or platelets numbers.

Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism.

Although it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified. A retrospective single-center study enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx), n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C), n=29). The patients had received L-T4 therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4 level (≥ 1.10 or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3) levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed. FT3 levels and FT3/FT4 ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4 ≥ 1.10 ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement therapy (P=0.018). In CeH, patients with median-lower normal levels of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support the target levels of serum FT4 as middle-upper normal levels during l-T4 replacement therapy in patients with CeH.

Evolution of glycated haemoglobin in adults on growth hormone replacement therapy

ObjectivesTo evaluate the effects of GH replacement therapy (GHR) for 3 years on glycated haemoglobin (HbA1c) and on the presence of dysglycaemia at any time during follow-up in Spanish adult patients with growth hormone deficiency (GHD). Study designA retrospective study of 41 patients with GHD was conducted using baseline and long-term data. Changes in HbA1c values during the first 3 years of GHR were studied in both the overall population and patients with or without dysglycaemia during follow-up. Dysglycaemia was defined as FPG≥100mg/dl and/or HbA1c≥5.7%. ResultsMean HbA1c value (5.4±0.4% at baseline) increased during the first and second years of GHR (HbA1c 5.5±0.4%, p=0.05, and 5.5±0.4%, p=0.006 respectively). This increase was not maintained during the third year (HbA1c 5.4±0.3%, p=0.107) of GHR. Twenty-eight patients (68.2%) had dysglycaemia during follow-up, 9 of them since baseline. In the 19 patients without baseline dysglycaemia, HbA1c increased during the first year and remained stable in the next 2 years (mean HbA1c 5.2±0.4% at baseline; 5.5±0.4% at 1 year, p<0.050; 5.4±0.4% at 2 years, p=0.004, and 5.4±0.4% at 3 years, p=0.016). In the 9 patients with baseline dysglycaemia, HbA1c did not significantly change during the 3 years of GHR therapy. ConclusionsHbA1c values increased during the first 2 years of GHR therapy. In patients with no dysglycaemia before treatment, HbA1c steadily increased over the 3 years. However, it did not change in patients with baseline dysglycaemia.

Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults: a retrospective cohort study.

Despite the well-known effects of GH/IGF1 signaling on the thyroid, few data are available on the risk of developing nodular goiter in hypopituitary subjects during GH replacement therapy (GHRT). We aimed to define the effects of GH therapy on thyroid volume (TV) and nodular growth. The records of 96 subjects (47 males and 49 females, median age 48 years) with GH deficit (GHD) were investigated. Seventy also had central hypothyroidism (CH). At the time of our retrospective evaluation, median treatment duration was 5 years. Pre-treatment TV was smaller in GHD patients than in healthy subjects (P=0.030). During GH treatment, TV significantly increased (P=0.016 for the entire group and P=0.014 in euthyroid GHD patients). Before starting GH therapy, 17 patients harbored thyroid nodules. During GH therapy, nodule size increased slightly in seven patients, and new thyroid nodules occurred in nine patients. Among the 79 patients without pre-existing thyroid nodules, 17 developed one or more nodules. There was no difference in the prevalence of CH in GHD patients with or without thyroid nodules (P=0.915; P=0.841, when patients with pre-therapy nodular goiter were excluded), the main predictor for nodule development being serum IGF1 (P=0.038). GHRT is associated with TV's increase in GHD patients. Thyroid nodules developed in 27% of patients, mainly in relation to pre-therapy IGF1 levels, independently of normal or impaired TSH stimulation.

Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults.

Isolated GH deficiency (IGHD) could provide a model to investigate the influence of GH deficiency per se and the effect of GH replacement therapy without the influence from other pituitary hormone deficiencies or their treatment. The aim of this study is to address the questions about differences between IGHD and multiple pituitary hormone deficiencies (MPHDs) in clinical presentation and in responsiveness to GH treatment. A nationwide surveillance study was carried out to describe the difference in the clinical presentation and responsiveness to GH treatment of patients with IGHD and MPHDs. The Dutch National Registry of GH Treatment in Adults was founded in 1998 to gain more insight into long-term efficacy and safety of GH therapy. Out of 2891 enrolled patients, 266 patients with IGHD at the start of GH treatment were identified and compared with 310 patients with MPHDs. Cardiovascular indices will be investigated at baseline and during long-term follow-up, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity. Patients with IGHD and MPHDs were demonstrated to be different entities at clinical presentation. Metabolically, patients with MPHDs had a larger waist circumference, lower HDL cholesterol level, and higher triglyceride level. The effect of GH treatment was comparable between patient groups. GH seems to protect against rising lipid levels and blood pressure, even after excluding patients using corresponding concomitant medication. The risk for cardiovascular disease or diabetes mellitus during follow-up was not different between patients with IGHD and MPHDs. Patients with IGHD had a less impaired metabolic profile than patients with MPHDs at baseline. Influence of other pituitary hormone replacement therapies on the effect of GH treatment is not demonstrated.

Evaluation of Asymmetric Dimethylarginine (ADMA) Levels in Children with Growth Hormone Deficiency

Ob­jec­ti­ve: To investigate serum asymmetric dimethylarginine (ADMA) levels in children with isolated growth hormone deficiency (GHD) and to determine the effect of GH replacement therapy on these levels.Methods: 31 patients diagnosed with isolated GHD and 29 age-and sex-matched healthy children were enrolled in the study. Height, weight and waist circumference were measured in all subjects. Fasting serum insulin-like growth factor-1 (IGF-1), IGF binding protein-3, glucose, insulin and lipid levels were evaluated. Serum ADMA levels were assessed using the enzyme-linked immunosorbent assay technique. The same evaluations were repeated on the 3rd and 6th months of treatment in 28 of the GHD cases.Results: There were no significant differences in ADMA levels between the patient and control groups [0.513±0.130 (0.291-0.820) µmol/L vs. 0.573±0.199 (0.241-1.049) µmol/L]. There was a positive correlation between serum ADMA and HbA1c levels in the control group. In the GHD cases, ADMA levels negatively correlated with high-density lipoprotein levels and positively correlated with low-density lipoprotein levels. There was also a significant increase in ADMA levels in patients receiving GH therapy compared to pre-treatment levels [serum ADMA level, 1.075±0.133 (0.796-1.303) µmol/L at the 3rd month and 0.923±0.121 (0.695-1.159) µmol/L at the 6th month of treatment]. There was a negative correlation between ADMA levels and homeostasis model assessment of insulin resistance values at the 6th month evaluation. There were no relationships between ADMA levels and age, sex, or pubertal state either before or during the treatment.Conclusion: Serum ADMA levels were found to be similar in patients with GHD and in healthy children. However, serum ADMA levels showed a significant increase in GHD patients following GH replacement therapy.

Clinical characteristics and effects of GH replacement therapy in adults with childhood-onset craniopharyngioma compared with those in adults with other causes of childhood-onset hypothalamic–pituitary dysfunction

Adults with childhood-onset (CO) craniopharyngioma (COCP) have poor quality of life (QoL) and clinical outcomes, but few studies have compared these patients with adults with other causes of CO hypothalamic-pituitary dysfunction. In this study, we compared baseline clinical characteristics and patient-reported outcomes before starting GH replacement therapy in adults with GH deficiency (GHD) due to COCP with those of adults either with CO idiopathic/congenital hypopituitarism (COH) or with CO extrasellar (COE) tumours, and evaluated the 1- and 5-year effects of GH replacement therapy. Retrospective analysis of the data recorded in KIMS (Pfizer International Metabolic Database) was carried out. Patients with COCP, COH and COE tumours were evaluated at baseline, and after 1 and 5 years of therapy. Compared with COH and COE patients, more COCP patients underwent surgery, had greater abnormalities of body composition and higher prevalence of pituitary hormone deficits (all P<0.001), but comparable fasting glucose, HbA1c, total cholesterol and LDL-cholesterol levels, marital status, parenthood, living arrangements, education, employment and annual sick-leave days. After 1 and 5 years of GH replacement therapy, similar changes were evident with regard to body composition, fasting glucose and HbA1c levels, QoL, and the level of and satisfaction with physical activity across the three groups. Adults with untreated COCP with GHD at baseline demonstrated more co-morbidities including greater abnormalities of body composition, pituitary hormone deficits and visual field defects. Overall, adults with COCP, COH and COE tumours responded comparably to short- and long-term GH replacement therapy, suggesting that patients with GHD due to COCP benefited from GH replacement therapy to a similar degree as those with other causes of CO hypothalamic-pituitary dysfunction did.

Efficacy and safety of growth hormone replacement therapy in Japanese adults with growth hormone deficiency: a post-marketing observational study

This large-scale observational study examined the long-term effectiveness and safety of growth hormone (GH) replacement therapy for adult GH deficiency (GHD) in Japanese clinical practice using the Hypopituitary Control and Complications Study database. The study included 402 GHD patients for safety analyses and a subset of 209 patients (149 adult-onset and 60 childhood-onset GHD patients) who had not previously received GH replacement therapy for the efficacy analyses. Data on clinical, metabolic, quality of life (QoL) characteristics, and all adverse events (AEs) were collected at baseline (start of GH treatment), 6 months, 1 year and 2 years. Over the observation period, there were improvements from baseline in insulin-like growth factor-I standard deviation scores (P<0.001), although the changes in metabolic parameters were minimal. QoL (Short Form-36) Z-scores significantly increased from baseline in both onset-type groups for several subscale domains (P<0.05). A total of 145 (36.1%) patients experienced ≥1 AE. Common AEs were hyperlipidaemia (2.7%) and hyperinsulinaemia (2.2%). Some patients experienced recurrent hypothalamic/pituitary tumour (events per 1000 patient-years: 2.78), new benign (0.93), malignant tumour (10.28) or other new tumour (0.93), new diabetes mellitus (7.45), and new stroke (3.71). Seven patients died during the observation period. Our safety findings are inconclusive about the associations between GH replacement and AEs, although the incidence of diabetes mellitus and cardiovascular events are similar to those reported in the Japanese general population. In conclusion, the key beneficial effects of GH replacement therapy for GHD are observed in routine clinical practice in Japan.

Quality of Life in Adult Hypopituitary Patients Treated for Growth Hormone Deficiency

Growth hormone (GH) affects all organ systems and several studies have also indicated an influence on health related quality of life (QoL). Assessment of QoL is therefore considered as one of several valid indicators of whether or not treatment with GH is beneficial. Two main types of QoL measures are generally used: disease-specific and generic. A combination of the two is generally advocated as they seem to be complementary. Methodologically, questionnaires must be correctly validated in the relevant context of language and a sufficient population based reference group. In this review, the previously published studies on the effects of GH replacement therapy on QoL in adults will be scrutinized. Although many of the studies on the influence of GH replacement on QoL assessment are either having a too short follow-up period, are uncontrolled, or using supra-physiological GH doses or inappropriate QoL instruments, there is a growing body of evidence for impaired QoL in GH deficient patients with improvement or normalisation after GH replacement.

Growth hormone, prolactin, and sexuality.

GH and PRL, although not considered as 'classi cal' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL in crease can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamus-pituitary-gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function.

Impact of growth hormone (GH) treatment on circulating Nt-proBNP concentrations and on cardiac function in adult GH-deficient patients

Severe adult growth hormone deficiency (AGHD) is associated with increased cardiovascular risk. We have therefore investigated levels of amino terminal pro-brain natriuretic peptide (Nt-proBNP), a well established biomarker for cardiac failure, in adult GHD patients before and after GH replacement therapy, and potential parallel variations in cardiac function. Nt-proBNP concentrations were determined at baseline and after GH treatment in two studies including 28 and 12 patients with severe AGHD, respectively. In the second study, a maximal exercise test and a doppler echocardiography were performed to assess cardiac functional parameters. At baseline, Nt-proBNP levels were higher in AGHD patients than in controls (median: 7.8 vs. 3.7 pmol/L; p < 0.01 in study 1; 8.4 vs. 4.1 pmol/L; p < 0.01 in study 2). Following GH treatment, Nt-proBNP levels decreased significantly in both studies. None of the AGHD patients had signs of cardiac dysfunction at baseline and no significant effect of GH replacement therapy was observed on cardiac functional parameters, independent of changes in Nt-proBNP. In conclusion, GH treatment markedly reduces Nt-proBNP concentrations in adult GHD patients without obvious parallel changes in cardiac functional parameters. These results suggest that Nt-proBNP may appear as a biomarker of GH status and GH treatment efficiency.

Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy

Liver dysfunction in adult hypopituitary patients with GH deficiency (GHD) has been reported and an increased prevalence of nonalcoholic fatty liver disease (NAFLD) has been suggested. The objective of the present study was to elucidate the pathophysiology of the liver in adult hypopituitary patients with GHD. We recruited 69 consecutive Japanese adult hypopituitary patients with GHD and examined the prevalence of NAFLD by ultrasonography and nonalcoholic steatohepatitis (NASH) by liver biopsy. Patients had been given routine replacement therapy except for GH. We compared these patients with healthy age-, gender-, and BMI-matched controls. We further analyzed the effect of GH replacement therapy on liver function, inflammation and fibrotic markers, and histological changes. The prevalence of NAFLD in hypopituitary patients with GHD was significantly higher than in controls (77 vs 12%, P<0.001). Of 16 patients assessed by liver biopsy, 14 (21%) patients were diagnosed with NASH. GH replacement therapy significantly reduced serum liver enzyme concentrations in the patients and improved the histological changes in the liver concomitant with reduction in fibrotic marker concentrations in patients with NASH. Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.