Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Faienza, Maria Felicia; Brunetti, Giacomina; Acquafredda, Angelo; Delvecchio, Maurizio; Lonero, Antonella; Gaeta, Alberto; Bulzis, Paola Suavo; Corica, Domenico; Velletri, Maria Rosa; Luca, Filippo De; Waśniewska, Małgorzata

doi:10.1159/000456546

Cited by 19 publications

(10 citation statements)

References 55 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, all research participants of eligible studies were girls diagnosed with CPP. The diagnostic criteria for CPP were as follows: (i) the onset of breast development (Tanner stage B2 or above) before 8 years of chronologic age; (ii) luteinizing hormone (LH) response to GnRH stimulation test (LH peak >5.0 IU/L, LH/follicle-stimulating hormone ratio >0.6); and (iii) no evidence of hypothalamic-pituitary organic lesions observed by magnetic resonance imaging (21,22). Second, eligible studies compared at least two interventions that included GnRHa alone, GnRHa+GH, or a control group.…”

Section: Study Selectionmentioning

confidence: 99%

Comparative Efficacy and Safety of Three Current Clinical Treatments for Girls with Central Precocious Puberty: A Network Meta-Analysis

Luo

et al. 2019

Endocrine Practice

View full text Add to dashboard Cite

“…However, it is worth mentioning that GnRH analogs treatment has been reported to be associated with a high risk of polycystic ovary syndrome (PCOS). [ 23 ] Our present case was obese accompanied by the IGT, which could also contribute to the development of PCOS. Furthermore, both early puberty and obesity have been documented to be associated with adverse long-term endocrine and metabolic outcomes, including hypertension, type 2 diabetes, stroke, cardiovascular mortality, and cancer.…”

Section: Discussionmentioning

confidence: 79%

A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty

Liu¹,

Fan²,

Gong³

2020

Medicine

View full text Add to dashboard Cite

Rationale: Central precocious puberty (CPP) is caused by the premature activation of the hypothalamic-pituitary-gonadal axis. Recently, the makorin ring finger protein 3 (MKRN3) mutations represent the most common genetic defects associated with CPP. However, the MKRN3 mutation is relatively rare in Asian countries. Here, we identified a novel heterozygous MKRN3 nonsense mutation (p. Gln363 ∗ ) causing CPP in a Chinese girl. Patient concerns: The index case is a 7-year-old Chinese girl who presented rapidly progressive precocious puberty with the onset of menstrual period 2 months after breast development, the advanced bone age (11 years), and the accelerated growth velocity (10 cm/year). Her basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, as well as the peak LH/FSH values after the gonadotropin-releasing hormone (GnRH) stimulation test were significantly elevated. Pelvic B ultrasound showed the presence of ovarian follicles with diameters ≥0.4 cm. Uterine length also indicated the onset of puberty. Contrast-enhanced magnetic resonance imaging (MRI) did not disclose any abnormality in the pituitary. Additionally, our present case was obese companies with impaired glucose tolerance (IGT) at the baseline assessment. Genetic analysis revealed a novel heterozygous nonsense mutation (c1087C>T; p. Gln363 ∗ ) in the maternally imprinted MKRN3 , which inherited from the girl's father. Diagnosis: Combined with the symptoms, hormonal data, and the results of the pelvic B ultrasound, the girl was diagnosed as CPP. Interventions: The girl has been treated with a GnRH analog (3.75 mg every 4 wks) for 1 year and 5 months. Outcomes: The puberty signs have since not progressed during the follow-up period, which indicates that the GnRH analogs treatment is effective. Lessons: This case was obese companied with IGT at the baseline assessment and exhibited stronger LH/FSH response to GnRH stimulation test. Therefore, clinicians should highlight the importance of weight management and the long-term follow-up to monitor the adverse health outcomes, especially for the polycystic ovary syndrome in later life.

show abstract

“…A cross-sectional retrospective study by Lazar et al also showed no metabolic derangements in GnRHa-treated female adults with CPP aged 30 to 50 years (10). Several studies during GnRHa treatment in children with CPP showed lower insulin sensitivity, expressed as the homeostatic model assessment of insulin resistance (5)(6)(7)(8). This might be explained by the difference in population as early puberty also increases the risk of diabetes (17).…”

Section: Discussionmentioning

confidence: 94%

“…In patients with central precocious puberty (CPP), a decrease in insulin sensitivity, expressed in the homeostatic model assessment of insulin resistance, was described during GnRHa treatment (5)(6)(7)(8). Gain in weight and fat mass during treatment with GnRHa was reported, potentially causing obesity in adulthood (9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

Longitudinal Study on Metabolic Health in Adults SGA During 5 Years After GH With or Without 2 Years of GnRHa Treatment

Goedegebuure

Steen

Kerkhof³

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

View full text Add to dashboard Cite

Background In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH. Methods A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and β-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans. Findings In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group. Interpretation This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood. Clinical trial registration ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389.

show abstract

“…m 2 ) with increased central adiposity (7). The main risk factors for development of PCOS manifest as atypical precocious puberty, premature pubarche, obesity, and metabolic syndromes in childhood (8, 9).…”

Section: Introductionmentioning

confidence: 99%

Circulating Endothelial Microparticles Reduce in Concentration Following an Exercise Programme in Women With Polycystic Ovary Syndrome

et al. 2019

View full text Add to dashboard Cite

Purpose: Endothelial dysfunction is a known comorbidity in women with polycystic ovary syndrome (PCOS). The aim was to assess if supervised, moderate intensity exercise could potentially impact markers of endothelial disruption; endothelial cell derived microparticles (EMP). Methods: The current study investigated the effects of a supervised 8-week moderate intensity exercise programme on EMP in women with PCOS ( n = 11) and control women free from any known disease ( n = 10). EMP were enumerated via specific antibody (CD105, CD106) labeling and flow cytometry. Results: CD105+MP significantly reduced in women with PCOS from pre to post-exercise programme, with CD105+ MP reducing from 2114 CD105+ MP per μl platelet free plasma (PFP) to 424 CD105+ MP per μl PFP ( p = 0.025). Control women showed no significant change in CD105+ MP ( p = 0.25) after completing the same exercise programme. CD106+ MP showed no change in either PCOS ( p = 0.95) or control groups ( p = 0.99). No significant correlations existed with the changes in EMP compared to body composition changes as a result of exercise. Conclusion: Supervised, moderate intensity exercise independent of substantial weight loss reduced circulating CD105+ MP, likely reflecting an improvement in endothelial function in women with PCOS compared to healthy control women. Additionally, EMP may be a useful marker for physical improvement in exercise programmes for clinical populations.

show abstract

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Cited by 19 publications

References 55 publications

Comparative Efficacy and Safety of Three Current Clinical Treatments for Girls with Central Precocious Puberty: A Network Meta-Analysis

A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty

Longitudinal Study on Metabolic Health in Adults SGA During 5 Years After GH With or Without 2 Years of GnRHa Treatment

Circulating Endothelial Microparticles Reduce in Concentration Following an Exercise Programme in Women With Polycystic Ovary Syndrome

Contact Info

Product

Resources

About