Abstract
Context
Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual.
Objective
To describe bone mass development in adolescents ...with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones.
Design
Observational prospective study.
Subjects
51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups.
Main Outcome Measures
Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers.
Results
At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment.
Conclusions
BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.
The role of gonadotrophin‐inhibitory hormone (GnIH) in the inhibition of the reproductive axis has been well‐established in birds and mammals. However, its role in other vertebrates, such as the ...teleost fish, remains controversial. In this context, the present study aimed to evaluate whether GnIH modulates the release of gonadotrophins and growth hormone (GH) in the cichlid fish Cichlasoma dimerus. First, we partially sequenced the precursor polypeptide for GnIH and identified three putative GnIH peptides. Next, we analysed the expression of this precursor polypeptide via a polymerase chain reaction in the reproductive axis of both sexes. We found a high expression of the polypeptide in the hypothalamus and gonads of males. Immunocytochemistry allowed the observation of GnIH‐immunoreactive somata in the nucleus posterioris periventricularis and the nucleus olfacto‐retinalis, with no differences between the sexes. GnIH‐immunoreactive fibres were present in all brain regions, with a high density in the nucleus lateralis tuberis and at both sides of the third ventricle. Finally, we performed in vitro studies on intact pituitary cultures to evaluate the effect of two doses (10−6 m and 10−8 m) of synthetic C. dimerus (cd‐) LPQRFa‐1 and LPQRFa‐2 on the release of gonadotrophins and GH. We observed that cd‐LPQRFa‐1 decreased β‐luteinising hormone (LH) and β‐follicle‐stimulating hormone (FSH) and also increased GH release to the culture medium. The release of β‐FSH was increased only when it was stimulated with the higher cd‐LPQRFa‐2 dose. The results of the present study indicate that cd‐LPQRFa‐1, the cichlid fish GnIH, inhibits β‐LH and β‐FSH release and stimulates GH release in intact pituitary cultures of C. dimerus. The results also show that cd‐LPQRF‐2 could act as an β‐FSH‐releasing factor in this fish species.
Abstract
Context
Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but ...currently no hormone references complement this method. Furthermore, previous studies have not explored the predictive value of endocrine profiling to determine female puberty onset.
Objective
To integrate US breast staging with hypothalamic-pituitary-gonadal hormone references and test the predictive value of an endocrine profile to determine thelarche.
Design Setting and Participants
Cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years.
Main Outcome Measures
Clinical and ultrasound breast evaluations were performed for all included girls. Blood samples were analyzed by immunoassay and ultrasensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E2) and estrone (E1) from the subpicomolar range.
Results
References for E2, E1, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin were constructed in relation to chronological age, Tanner stages, and US breast stages. An endocrine profile index score derived from principal component analysis of these analytes was a better marker of puberty onset than age or any individual hormone, with receiver-operating characteristic area under the curve 0.91 (P < 0.001). Ultrasound detection of nonpalpable glandular tissue in 14 out of 264 (5.3%) girls with clinically prepubertal presentation was associated with significantly higher median serum levels of E2 (12.5 vs 4.9 pmol/L; P < 0.05) and a distinct endocrine profile (arbitrary units; P < 0.001).
Conclusions
We provide the first hormone references for use with US breast staging and demonstrate the application of endocrine profiling to improve detection of female puberty onset.
Amyloids are highly organized cross-β-sheet-rich protein or peptide aggregates that are associated with pathological conditions including Alzheimer's disease and type II diabetes. However, amyloids ...may also have a normal biological function, as demonstrated by fungal prions, which are involved in prion replication, and the amyloid protein Pmel17, which is involved in mammalian skin pigmentation. We found that peptide and protein hormones in secretory granules of the endocrine system are stored in an amyloid-like cross-β-sheet-rich conformation. Thus, functional amyloids in the pituitary and other organs can contribute to normal cell and tissue physiology.
In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated infection (coronavirus disease 2019 COVID‐19) developed rapidly and has turned into ...a global pandemic. Although SARS‐CoV‐2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID‐19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID‐19 patients for virus detection and semen characteristics analysis. No SARS‐CoV‐2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex‐related hormone levels between 119 reproductive‐aged men with SARS‐CoV‐2 infection and 273 age‐matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID‐19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C‐reactive protein levels in COVID‐19 patients. It's the first report about semen assessment and sex‐hormone evaluation in reproductive‐aged male COVID‐19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID‐19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow‐up.
Highlights
Sex‐hormone levels were evaluated in reproductive‐aged male COVID‐19 patients. Semen assessment was performed in recovering male COVID‐19 patients. No SARS‐CoV‐2 virus was found in semen from recovering COVID‐19 patients.
A consensus has been reached on the preferred primary outcome of all infertility treatment trials, which is the cumulative live birth rate (CLBR). Some recent randomized controlled trials (RCTs) and ...retrospective studies have compared the effectiveness of GnRH-antagonist and GnRH-agonist protocols but showed inconsistent results. Studies commonly used conservative estimates and optimal estimates to described the CLBR of one incomplete assisted reproductive technology (ART) cycle and there are not many previous studies with data of the complete cycle to compare CLBRs in GnRH-antagonist versus GnRH-agonist protocols.
A total of 18,853 patients have completed their first IVF cycle including fresh and subsequent frozen-thawed cycles during 2016-2019, 16,827 patients were treated with GnRH-a long and 2026 patients with GnRH-ant protocol. Multivariable logistic analysis was used to evaluate the difference of GnRH-a and GnRH-ant protocol in relation to CLBR. Utilized Propensity Score Matching(PSM) for sampling by up to 1:1 nearest neighbor matching to adjust the numerical difference and balance the confounders between groups.
Before PSM, significant differences were observed in baseline characteristics and the CLBR was 50.91% in the GnRH-a and 33.42% in the GnRH-ant (OR = 2.07; 95%CI: 1.88-2.28; P < 0.001). Stratified analysis showed the CLBR of GnRH-ant was lower than GnRH-a in suboptimal responders(46.89 vs 27.42%, OR = 2.34, 95%CI = 1.99-2.74; P < 0.001) and no differences of CLBR were observed in other patients between protocols. After adjusting for potential confounders, multivariable logistic analysis found the CLBR of GnRH-ant group was lower than that of GnRH-a group (OR = 2.11, 95%CI:1.69-2.63, P < 0.001). After PSM balenced the confounders between groups, the CLBR of GnRH-a group was higher than that of GnRH-ant group in suboptimal responders((38.61 vs 28.22%, OR = 1.60, 95%CI = 1.28-1.99; P < 0.001) and the normal fertilization rate and number of available embryo in GnRH-a were higher than these of GnRH-ant groups in suboptimal responders (77.39 vs 75.22%; 2.86 ± 1.26 vs 2.61 ± 1.22; P < 0.05). No significant difference was observed in other patients between different protocols.
It is crucial to optimize the utilization of protocols in different ovarian response patients and reconsider the field of application of GnRH-ant protocols in China.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Objective
To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TU2670, a novel orally active, nonpeptide gonadotropin-releasing hormone (GnRH) antagonist ...administered to healthy female participants.
Methods
This was a first-in-human, multicenter, phase 1, randomized, double-blind, placebo-controlled, single-dose ascending trial that took place in multiple medical centers. A total of 16 healthy premenopausal women (23 to 45 years of age) were randomized and received 20, 40, 80, and 160 mg TU2670 (GnRH antagonist) or placebo 7 days (±1 day) after the onset of menstrual bleeding. We performed a noncompartmental analysis for pharmacokinetic parameters and calculated relative minimum concentration values (Cmin, % Baseline) of serum pharmacodynamic (PD) markers (luteinizing hormone LH, follicle-stimulating hormone FSH, and estradiol).
Results
There were no significant differences among treatments with respect to vital signs, electrocardiography, adverse events, ovulation test results, and ultrasonography. The median Tmax of TU2670 occurred 0.75 to 1.00 hours after dosing, and concentrations then declined, with a mean apparent half-life (t1/2) of 3.0 to 5.9 hours. AUClast (17.7-417.9 ng·h/mL) and Cmax (8.1-95.4 ng/mL) increased in a dose-dependent manner. The PD analysis after a single administration of TU2670 revealed dose-dependent suppression of LH, FSH, and estradiol. Maximal suppression of the pre-dose baseline (%) was 58% to 82% at 6 to 8 hours for LH, 28% to 39% at 6 to 12 hours for FSH, and 34% to 82% at 12 to 24 hours for estradiol.
Conclusion
The single administration of TU2670 in healthy premenopausal women was well tolerated and resulted in the dose-dependent suppression of LH, FSH, and estradiol, suggesting rapid and significant inhibition of pituitary and ovarian hormones.
Highlights ► Review of the ever expanding members of the CHH-superfamily peptide hormones. ► Details gene, transcript, hormone structures, functions, expression, signaling. ► Highlights future ...research directions and challenges.
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