This nationwide population-based study assessed the long-term risk of cardiovascular events in patients who had received rhGH therapy during childhood and adolescence. The study cohort comprised 3.408 subjects treated under the GHD, SGA or ISS indications, and 50 036 age-, sex-, and region-based matched controls. Median follow-up was 14.9 years (to age 25 years) with a total of 795 125 person-years. Patients in each diagnostic group had a significant higher risk for cardiovascular events than controls (hazard ratio 1.69; 95% CI, 1.302.19), especially women (HR, 2.95; 95%CI, 1.313.20) and those treated for SGA (HR, 1.97, %CI, 1.28-3.04). The increased risk was found in all treated groups and was associated with longer therapy duration and cumulative rhGH dose. The most common severe cardiovascular events were ischemic heart disease, cardiomyopathy and stroke.
A secular trend for earlier menarcheal age has been established in girls but there are few studies of pubertal timing for boys.To determine if there is a secular trend for earlier pubertal timing among boys.For this population-based retrospective cohort study conducted in Gothenburg, Sweden, we collected heights and weights from school health records for boys born consecutively from January 1 and onwards in 1947 and every 5 years from 1951 to 1996 (n = 375 for each birth cohort from 1947-1991, n = 340 for the birth cohort in 1996, and n = 4090 for the total cohort). We estimated age at the peak height velocity (PHV), the maximum growth velocity during puberty, and childhood body mass index (BMI) at age 8 years for all study participants. The data were analyzed during 2018 and 2019. Boys were eligible if they had a complete personal identity number and data to calculate their age at PHV and childhood BMI. Approximately 2.4% of the original study population was excluded because they lacked a personal identity number, and in the remaining study population, 4090 (69%) had sufficient data to calculate childhood BMI and age at PHV.The exposure was birth year and a potential confounding factor was childhood BMI.The outcome was age at PHV.Of the 4090 participants, most were white and the mean (SD) age at PHV was 13.9 (1.1) years. A linear regression model revealed a significant association between year of birth and age at PHV. Age at PHV was 1.5 months earlier for every decade increase in birth year (95% CI, -1.72 to -1.19; P < .001). After adjusting for childhood BMI, age at PHV was 1.2 months earlier per decade increase in birth year (95% CI, -1.41 to -0.89). All analyses were repeated in the subgroup of boys born in Sweden and with parents born in Sweden with similar results, indicating that the secular trend was not explained by demographic changes in the population between 1947 and 1996.We provide evidence of a secular trend for earlier pubertal timing in boys that is partially explained by an increased childhood BMI, but other factors that are unknown contribute.
Growth hormone (GH) is prescribed for an increasing range of indications, but there has been concern that it might raise cancer risk. Published data are limited. To examine cancer risks in relation to GH treatment. Cohort study. Population-based. Cohort of 23,984 patients treated with recombinant human GH (r-hGH) in eight European countries since this treatment was first used in 1984. Cancer expectations from country-specific national population statistics. Cancer incidence and cancer mortality. Incidence and mortality risks in the cohort were raised for several cancer sites, largely consequent on second primary malignancies in patients given r-hGH after cancer treatment. There was no clear raised risk in patients with growth failure without other major disease. Only for bone and bladder cancers was incidence significantly raised in GH-treated patients without previous cancer. Cancer risk was unrelated to duration or cumulative dose of r-hGH treatment, but for patients treated after previous cancer, cancer mortality risk increased significantly with increasing daily r-hGH dose (P trend < 0.001). Hodgkin lymphoma (HL) incidence increased significantly with longer follow-up (P trend = 0.001 for patients overall and 0.002 for patients without previous cancer). Our results do not generally support a carcinogenic effect of r-hGH, but the unexplained trend in cancer mortality risk in relation to GH dose in patients with previous cancer, and the indication of possible effects on bone cancer, bladder cancer, and HL risks, need further investigation.
<b><i>Introduction:</i></b> Growth hormone (GH) is a central hormone for regulating linear growth during childhood and also highly involved in the metabolism of lipids, carbohydrates, and protein. However, few studies report on how treatment with GH during childhood influences metabolic parameters. Our aim was to investigate metabolic effects of different doses of GH in short children with GH peak levels in the low to normal range. <b><i>Design:</i></b> Thirty-five prepubertal short children (<−2.5 SDS), aged 7–10 years, with peak levels of GH between 7 and 14 μg/L during an arginine-insulin tolerance test, were randomized to 3 different doses (11/33/100 μg/kg/day) of GH treatment for 2 years. Auxological and metabolic investigations were performed. These included metabolites in blood and interstitial microdialysis fluid, dual-energy X-ray absorptiometry, frequently sampled intravenous glucose tolerance test (FSIVGTT), and stable isotope examinations of rates of glucose production and lipolysis. <b><i>Results:</i></b> At 24 months, the high-dose group (HD) had higher fasting insulin compared with the standard-dose (SD) and low-dose (LD) groups (HD: 111.7 vs. SD: 61.2 and LD: 46.0 pmol/L [<i>p</i> < 0.001]) and showed signs of insulin resistance (HOMA-IR, HD: 4.20 vs. SD: 2.17 and LD: 1.71 (LD) [<i>p</i> < 0.001]). The FSIVGTT also demonstrated higher acute insulin response (<i>p</i> < 0.05). Few other metabolic differences were found at 24 months, but a decreased insulin sensitivity index (Si) could already be seen at 12 months for both SD and HD compared with the LD group (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> Treatment with GH resulted in a dose-dependent decrease in insulin sensitivity, demonstrated by higher levels of fasting insulin and signs of insulin resistance in both HOMA indices and FSIVGTT examinations.
Background Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited. Methods A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020. Results 53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26). Conclusion No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.
Concerns about the cardiovascular safety of recombinant human growth hormone (rhGH) treatment in childhood have recently been raised; however, long-term studies are limited.To investigate the long-term risk of overall and severe cardiovascular events in patients previously treated with rhGH in childhood and whether there is an association with treatment duration or dose.This nationwide population-based cohort study included patients treated with rhGH during childhood from January 1, 1985, to December 31, 2010, in Sweden, with follow-up through December 31, 2014. Included patients were treated with rhGH owing to isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS). For each patient, 15 age-, sex-, and region-based matched control individuals were randomly selected from the general population as a comparison group. Data on cardiovascular outcomes and covariates including gestational age, birth weight, birth length, socioeconomic status, and height were obtained through linkage with several health care and population-based registers. Data were analyzed from January 1, 1985, to December 31, 2014.Treatment with rhGH during childhood and adolescence (aged 0-18 years).The primary outcome was the first cardiovascular event recorded after the start of follow-up, and the secondary outcome was the first severe cardiovascular event.A total of 53 444 individuals (3408 patients and 50 036 controls; 67.7% men; mean [SD] age at study end, 25.1 [8.2] years) were followed up for as long as 25 years (median follow-up, 14.9 [range, 0-25] years; total, 795 125 person-years). Among 1809 recorded cardiovascular events, the crude incidence rates were 25.6 events per 10 000 person-years for patients and 22.6 events per 10 000 person-years for controls. The adjusted hazard ratio (HR) for all cardiovascular events was higher in patients compared with controls (HR, 1.69; 95% CI, 1.30-2.19), especially for women (HR, 2.05; 95% CI, 1.31-3.20) compared with men (HR, 1.55; 95% CI, 1.12-2.13). All subgroups had increased HRs (SGA, 1.97 [95% CI, 1.28-3.04]; GHD, 1.66 [95% CI, 1.21-2.26]; and ISS, 1.55 [95% CI, 1.01-2.37]). Longer duration of rhGH treatment (HR, 2.08; 95% CI, 1.35-3.20) and total cumulative dose (HR, 2.05; 95% CI, 1.18-3.55) were associated with higher risk for overall cardiovascular disease. The adjusted HR for severe cardiovascular disease was 2.27 (95% CI, 1.01-5.12).In this cohort study, treatment with rhGH during childhood due to GHD, SGA, or ISS was associated with increased risks of cardiovascular events in early adulthood, particularly in women; however, conclusions of causality are still limited and the absolute risk remains low.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)