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Reproductive control in mammals, particularly in beef production systems, is crucial for managing behaviors driven by sex steroids, which can cause biosecurity issues, reduced weight gain, and decreased meat quality. Additionally, controlling sexual activity in females prevents unwanted pregnancies when both sexes are housed together for fattening. Surgical castration in cattle, commonly performed under field conditions, is associated with significant welfare concerns due to pain and infection risks. Furthermore, castrating female cattle in the field is often impractically expensive. Hence, new reproductive control methods that prioritize animal welfare and are suitable for both sexes are essential. Immunocastration (IC), which involves vaccination against the GnRH-I hormone, has emerged as a promising alternative, demonstrating efficacy and safety in various species. Immunocastration has proven to be an effective alternative to surgical castration in controlling reproduction and promoting animal welfare in several species. This study aims to evaluate the safety, immunogenicity, immunocastration effect, and productive impact of a novel IC vaccine developed in Chile for female cattle. Two consecutive trials were conducted, the first under controlled conditions and the second under field conditions. The results demonstrated that the new vaccine is safe and effective for use in beef cattle, inducing specific immunity against GnRH-I, reducing gonadal functionality, and improving productive parameters. These findings suggest that this new IC vaccine can significantly benefit the beef cattle industry by providing a welfare-friendly and efficient method of reproductive control.
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Kallmann syndrome is an anosmic variety of GnRH (gonadotropin-releasing hormone) deficiency. A young adult male with anosmia since childhood presented with features of failed sexual maturation and underwent an ultrasound of the genital system and an MRI (magnetic resonance imaging) of the brain. MRI revealed absent olfactory bulbs in bilateral olfactory grooves with hypoplastic olfactory sulci on both sides. Ultrasound showed atrophic testes, while the anterior pituitary appeared normal on MRI. The clinical, hormonal, and imaging findings were characteristic of Kallmann syndrome. MRI serves as a crucial tool in its diagnosis.
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OBJECTIVE: To compare the ongoing pregnancy rate per initiated cycle between patients with functional hypothalamic amenorrhea and patients with congenital hypogonadotropic hypogonadism treated with pulsatile GnRH administration. DESIGN: Retrospective monocentric cohort study conducted at the University Hospital of Lille from 2004 to 2022. PATIENT(S): 141 patients diagnosed with central supra-pituitary amenorrhea during infertility evaluation and subsequently treated with pulsatile GnRH therapy. 111 and 30 patients were diagnosed with functional hypothalamic amenorrhea or congenital hypogonadotropic hypogonadism, respectively. EXPOSURE(S): Pulsatile GnRH administration MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate per initiated cycle. RESULT(S): Ongoing pregnancy rates per initiated cycle were comparable between groups: 21.5% in the functional hypothalamic amenorrhea group versus 22% in the congenital hypogonadotropic hypogonadism group; p=0.537. Comparison of baseline characteristics showed a more pronounced FSH deficiency in patients with congenital hypogonadotropic hypogonadism than in those with functional hypothalamic amenorrhea: 2.55 [0.6 - 4.92] versus 4.80 [3.90 - 5.70] UI/L; p<0.001. Within the congenital hypogonadotropic hypogonadism group, basal FSH level was positively associated with the occurrence of ongoing pregnancies (OR= 1.57; CI95%: 1.11;2.22; p=0.010). In the congenital hypogonadotropic hypogonadism group the duration of treatment was higher than in the functional hypothalamic amenorrhea group: 23.59 (±8.02) versus 18.16 (±7.66) days, p<0.001. CONCLUSION: Baseline FSH is lower in patients with congenital hypogonadotropic hypogonadism than in patients with functional hypothalamic amenorrhea. The lower the FSH, the lower the chance of pregnancy in patients with congenital hypogonadotropic hypogonadism. These patients also require more days of GnRH administration. However, the rate of ongoing pregnancies is comparable between the two groups.
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[This corrects the article DOI: 10.3389/fvets.2024.1410371.].
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BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice. METHOD AND RESULT: Immunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice. CONCLUSION: This study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals.
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Hormona Liberadora de Gonadotropina , Maduración Sexual , Animales , Femenino , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/metabolismo , Ratones , Maduración Sexual/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismo , Poliaminas/metabolismo , Envejecimiento , Ovario/efectos de los fármacos , Ovario/metabolismo , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
The increase in the incidence of dementia over the last century correlates strongly with the increases in post-reproductive lifespan during this time. As post-reproductive lifespan continues to increase it is likely that the incidence of dementia will also increase unless therapies are developed to prevent, slow or cure dementia. A growing body of evidence implicates age-related endocrine dyscrasia and the length of time that the brain is subjected to this endocrine dyscrasia, as a key causal event leading to the cognitive decline associated with aging and Alzheimer's disease (AD), the major form of dementia in our society. In particular, the elevations in circulating gonadotropins, resulting from the loss of gonadal sex hormone production with menopause and andropause, appear central to the development of AD neuropathology and cognitive decline. This is supported by numerous cell biology, preclinical animal, and epidemiological studies, as well as human clinical studies where suppression of circulating luteinizing hormone and/or follicle-stimulating hormone with either gonadotropin-releasing hormone analogues, or via physiological hormone replacement therapy, has been demonstrated to halt or significantly slow cognitive decline in those with AD. This review provides an overview of past and present studies demonstrating the importance of hypothalamic-pituitary-gonadal hormone balance for normal cognitive functioning, and how targeting age-related endocrine dyscrasia with hormone rebalancing strategies provides an alternative treatment route for those with AD.
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Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.
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Tasa de Natalidad , Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Recuperación del Oocito , Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Humanos , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Adulto , Recuperación del Oocito/métodos , Inducción de la Ovulación/métodos , Estudios Retrospectivos , Embarazo , Estudios de Casos y Controles , Fertilización In Vitro/métodos , Síndrome de Hiperestimulación Ovárica/prevención & control , Síndrome de Hiperestimulación Ovárica/epidemiología , Nacimiento Vivo/epidemiología , Índice de Embarazo , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Taiwán/epidemiología , Inyecciones de Esperma Intracitoplasmáticas/métodosRESUMEN
OBJECTIVES: To observe the therapeutic efficacy of high-intensity focused ultrasound (HIFU) combined with different pharmacological treatments for adenomyosis. MATERIALS AND METHODS: A total of 126 patients with adenomyosis who underwent HIFU combined with pharmacological treatment were retrospectively reviewed. Patients were treated with either dienogest (DNG) (Group A, N = 38) or GnRH-a (Group B, N = 88) for three months after HIFU, and received levonorgestrel-releasing intrauterine systems (LNG-IUS) at the end of the third month. Visual Analog Scale (VAS) and Pictorial Blood Loss Assessment Chart (PBAC) scores were used for evaluating symptom improvement. RESULTS: After propensity score matching (1:2), 38 patients were included in Group A and 76 in Group B. All patients showed significant improvement in VAS and PBAC scores after HIFU, but the PBAC score of Group A was significantly higher than that of patients in Group B at 18 months [11.50 (1.00, 29.50) vs. 0.00 (0.00, 16.50), p < 0.01] and 24 months [4.00 (0.25, 27.75) vs. 0.00 (0.00, 12.75), p = 0.04] after HIFU. Furthermore, patients in Group B had a greater uterine volume reduction at 24 months after HIFU than that of patients in Group A [51.00 (27.00, 62.00) vs. 30.00 (17.00, 42.75, p = 0.02)]. However, the adverse effects in Group A were lower than those in Group B [7 (15.79) vs. 35 (46.05), p < 0.01]. No significant difference was observed in the recurrence rate between the two groups. CONCLUSIONS: HIFU combined with DNG and LNG-IUS is a safe and effective treatment for patients with adenomyosis.
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Adenomiosis , Ultrasonido Enfocado de Alta Intensidad de Ablación , Humanos , Femenino , Adenomiosis/terapia , Adenomiosis/tratamiento farmacológico , Adenomiosis/cirugía , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Adulto , Persona de Mediana Edad , Hormona Liberadora de Gonadotropina/uso terapéutico , Estudios Retrospectivos , Nandrolona/análogos & derivados , Nandrolona/uso terapéutico , Nandrolona/farmacología , Terapia Combinada/métodos , Levonorgestrel/uso terapéutico , Levonorgestrel/administración & dosificación , Resultado del TratamientoRESUMEN
Reproductive function in mammals depends on the ability of progesterone to suppress pulsatile gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in a homeostatic negative feedback loop. Previous research identified that cells upstream from GnRH neurons expressing the nuclear progesterone receptor (PGR) are required for progesterone-negative feedback. However, the identity of these cells and the mechanism by which they reduce GnRH/LH pulsatile secretion is unknown. We aimed to address the hypothesis that PGR expressed by a neural population in the arcuate nucleus recently identified as the GnRH pulse generator, cells expressing Kisspeptin, Neurokinin B, and Dynorphin (KNDy cells), mediate progesterone negative feedback. To achieve this, we utilized female mice with the PGR gene conditionally deleted from kisspeptin cells (KPRKO mice) and observed a substantial decrease in the percentage of KNDy neurons co-expressing PGR mRNA (11% in KPRKO mice versus 86% in wildtype mice). However, KPRKO mice did not display changes in the frequency or amplitude of LH pulses in diestrus or estrus, nor in the ability of exogenous progesterone to blunt a post-castration rise in LH. Further, mRNA expression of arcuate kisspeptin and dynorphin, which are excitatory and inhibitory to GnRH secretion, respectively, remained unaltered in KPRKO mice compared to wildtype controls. Together, these findings show that the near-complete loss of PGR signaling from KNDy cells does not impact negative feedback regulation of GnRH pulse generation in mice, suggesting that feedback through this receptor can occur via a small number of KNDy cells or a yet unidentified cell population.
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This study evaluated the use of the GnRH agonist hormone, deslorelin, to control the follicular population before initiating multiple ovulation and embryo transfer (MOET) treatment. Twenty-four cross-bred Santa Inês ewes, aged between 2 and 4 years, were randomly assigned to either a control group (n = 11) or a treated group (n = 13). All ewes received an intravaginal device containing 60 mg of medroxyprogesterone acetate on day 0, and a new device on day 7, which remained in place until day 14. Additionally, the ewes were administered 125 µg of cloprostenol on day 7. The superovulatory treatment involved administering 200 mg of pFSH, divided into eight decreasing doses at 12-h intervals starting on day 12. On day 14, 300 IU of eCG was administered. In the deslorelin group, three doses of 100 µg of deslorelin were administered starting on day 3 after the insertion of the vaginal device, with subsequent doses given at 72-h and 144-h intervals. Natural mating was performed 36 h after the removal of the progesterone implant using males with proven fertility. Embryo collection took place on the 6th day after mating, and the recovered structures were quantified and evaluated for quality and developmental stage. Transrectal ultrasonography was conducted on days 12, 16 and 21 to evaluate the ovaries, specifically to assess the ovarian follicular population and the presence of the corpus luteum. Ewes in the control group had higher embryo recovery rates (p < .01) compared to the treated group (5.2 ± 0.8 vs. 1.1 ± 0.8), with differences observed primarily in the number of morulae. The number of corpus luteum observed during the laparotomy on day 21 was significantly higher (p < .01) in the control group (10.44 vs. 4.5 corpus luteum per ewe). Yet, the treated group had a significantly higher number of follicles (p < .05) on the first day of pFSH application (5.5 vs. 3.0 follicles per ewe). In conclusion, although the inclusion of deslorelin in the superovulation protocol resulted in increased synchronization of oestrus and follicle number, it did not lead to an increase in the number of corpus luteum or harvested embryos.
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Transferencia de Embrión , Hormona Folículo Estimulante , Superovulación , Pamoato de Triptorelina , Animales , Femenino , Pamoato de Triptorelina/análogos & derivados , Pamoato de Triptorelina/farmacología , Pamoato de Triptorelina/administración & dosificación , Superovulación/efectos de los fármacos , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/administración & dosificación , Transferencia de Embrión/veterinaria , Cloprostenol/farmacología , Cloprostenol/administración & dosificación , Embarazo , Ovario/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Oveja Doméstica , Ovinos/fisiología , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/administración & dosificación , Acetato de Medroxiprogesterona/farmacología , Acetato de Medroxiprogesterona/administración & dosificaciónRESUMEN
Background: Estrus synchronization is an important assisted reproductive technology to improve the reproductive performance in ewes. Various protocols have been used with variable success rates, however; literature regarding field applicable estrus synchronization is meagre. Aims: The present study was designed with the aim to evaluate the estrus synchronization protocols on reproductive performance in ewes using different hormones. Methods: Experimental ewes were divided randomly into three groups (n=15). Ewes of all groups received intravaginal sponge for 12 days. Subsequently, NP4-GnRH and NP4-eCG groups received 8 µg of buserelin acetate or 200 IU of eCG intramuscularly, respectively on day 12 whereas NP4-Insulin group received insulin 0.2 IU/kg body weight subcutaneously for three consecutive days started on the day of sponge removal. Estrus detection commenced 24 h after sponge removal in NP4-GnRH and NP4-eCG groups and 24 h following last injection of insulin in NP4-Insulin group. The ewes in estrus were separated and pen mated. The conception rate was determined by ultrasonography. Results: The estrus response and conception rates were 71.43, 92.86 and 53.85%, and 70.00, 84.61, and 71.43%, respectively in NP4-GnRH, NP4-eCG, and NP4-Insulin groups. The lambing rates were the same as the conception rates. The single and multiple birth rates were 71.41, 36.36 and 60.0%, and 28.57, 63.64, and 40.0% whereas prolificacy was 128.57, 190.91, and 140.00%, respectively in NP4-GnRH, NP4-eCG, and NP4-Insulin groups. Conclusion: In conclusion, the estrus synchronization protocol including intravaginal progesterone sponge and eCG was found to be more effective under field conditions.
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Herein, we evaluated the effects of Gonadotropin hormone-releasing hormone (GnRH) administration 84 h after medroxyprogesterone acetate (MAP) sponge removal on follicular growth, ovulation timing, and pregnancy per artificial insemination (AI) in cosynchronized postpartum Nili Ravi buffaloes. In this study, 58 Nili Ravi postpartum buffaloes (DIM = 103 ± 1.64) were randomly divided into two treatment groups (n = 29/treatment): GnRH-TAI-84 and TAI-84. All buffaloes were administered a MAP sponge for seven days. Upon MAP sponge removal, all the subjects received prostaglandin F2α (PGF2α), and Timed AI (TAI) was performed 84 hours after sponge removal. In the GnRH-TAI-84 group, the buffaloes received GnRH alongside insemination, whereas in the TAI-84 group, the buffaloes were inseminated without GnRH administration. Follicle diameter and blood estradiol levels were measured every 6 h from 72-108 h after MAP sponge removal. The animals were checked for pregnancy using ultrasonography 40 days after AI. Animals subjected to the GnRH-TAI-84 protocol had a higher follicular growth rate and preovulatory follicle size than those in the TAI-84 group. The follicular diameter was also larger in animals that received GnRH-TAI-84 than in those that received TAI-84 90 and 96 h after MAP sponge removal. Buffaloes in the GnRH-TAI-84 group had lower estradiol concentrations at 90, 96, 102, and 108 h than those in the TAI-84 group. Ovulation in GnRH-TAI-84 buffaloes occurred 11 h earlier than that in buffaloes from the TAI-84 group. A shorter interval between AI and ovulation in GnRH-TAI-84 buffaloes (14 h vs. 25 h) led to greater pregnancies per AI (62% vs. 17%) compared to buffaloes from the TAI-84 group.
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RESEARCH QUESTION: Does luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol? METHODS: Retrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups. RESULTS: In patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379-10.643, P < 0.05). CONCLUSIONS: LHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes.
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Gonadotropina Coriónica , Transferencia de Embrión , Hormona Liberadora de Gonadotropina , Hormona Luteinizante , Reserva Ovárica , Inducción de la Ovulación , Índice de Embarazo , Humanos , Femenino , Embarazo , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Hormona Luteinizante/sangre , Gonadotropina Coriónica/administración & dosificación , Gonadotropina Coriónica/uso terapéutico , Adulto , Estudios Retrospectivos , Reserva Ovárica/efectos de los fármacos , Reserva Ovárica/fisiología , Inducción de la Ovulación/métodos , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Antagonistas de Hormonas/uso terapéutico , Antagonistas de Hormonas/administración & dosificación , Resultado del Tratamiento , Infertilidad Femenina/terapia , Infertilidad Femenina/sangre , Infertilidad Femenina/tratamiento farmacológico , Resultado del Embarazo/epidemiologíaRESUMEN
Neurons co-expressing kisspeptin, neurokinin B, and dynorphin A (KNDy neurons), located in the arcuate nucleus (ARC) of the hypothalamus, are indicated to be the gonadotropin-releasing hormone (GnRH) pulse generator. Dynorphin A is reported to suppress GnRH pulse generator activity. Nalfurafine is a selective agonist of the κ-opioid receptor (KOR), a receptor for dynorphin A, clinically used as an anti-pruritic drug. This study aimed to evaluate the effects of nalfurafine on GnRH pulse generator activity and luteinizing hormone (LH) pulses using female goats. Nalfurafine (0, 2, 4, 8, or 16 µg/head) was intravenously injected into ovariectomized Shiba goats. The multiple unit activity (MUA) in the ARC area was recorded, and plasma LH concentrations were measured 2 and 48 h before and after injection, respectively. The MUA volley interval during 0-2 h after injection was significantly increased in the nalfurafine 8 and 16 µg groups compared with the vehicle group. In 0-2 h after injection, the number of LH pulses was significantly decreased in the nalfurafine 8 and 16 µg groups, and the mean and baseline LH were significantly decreased in all nalfurafine-treated groups (2, 4, 8, and 16 µg) compared with the vehicle group. These results suggest that nalfurafine inhibits the activity of the GnRH pulse generator in the ARC, thus suppressing pulsatile LH secretion. Therefore, nalfurafine could be used as a reproductive inhibitor in mammals.
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Núcleo Arqueado del Hipotálamo , Cabras , Hormona Liberadora de Gonadotropina , Morfinanos , Receptores Opioides kappa , Compuestos de Espiro , Animales , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/metabolismo , Femenino , Compuestos de Espiro/farmacología , Compuestos de Espiro/administración & dosificación , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/agonistas , Morfinanos/farmacología , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Kisspeptinas/metabolismo , Dinorfinas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuroquinina B/metabolismoRESUMEN
Ovarian function is controlled by pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which in turn are governed by gonadotropin releasing hormone (GnRH) secreted from the brain. A fundamental principle of reproductive axis regulation is negative feedback signaling by gonadal sex steroids back to the brain to fine-tune GnRH and gonadotropin secretion. Endogenous negative feedback effects can be mimicked by exogenous steroid treatments, including androgens, in both sexes. Indeed, a growing number of clinical and animal studies indicate that high levels of exogenous androgens, in the typically male physiological range, can inhibit LH secretion in females, as occurs in males. However, the mechanisms by which male-level androgens inhibit GnRH and LH secretion still remain poorly understood, and this knowledge gap is particularly pronounced in transgender men (individuals designated female at birth but identifying as male). Indeed, many transgender men take long-term gender-affirming hormone therapy that mimics male-level testosterone levels. The impact of such gender-affirming testosterone on the reproductive axis, both at the ovarian and neuroendocrine level, is a long-understudied area that still requires further investigation. Importantly, the few concepts of androgen actions in females mostly come from studies of polycystic ovary syndrome, which does not recapitulate a similar androgen milieu or a pathophysiology of inhibited LH secretion as occurs in testosterone-treated transgender men. This review summarizes clinical evidence indicating that exogenous androgens can impair neuroendocrine reproductive function in both female individuals and transgender men and highlights emerging experimental data supporting this in recently developed transgender rodent models.
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Andrógenos , Sistemas Neurosecretores , Reproducción , Humanos , Femenino , Masculino , Andrógenos/farmacología , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/metabolismo , Sistemas Neurosecretores/fisiología , Reproducción/efectos de los fármacos , Reproducción/fisiología , Animales , Personas Transgénero , Hormona Luteinizante/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/fisiologíaRESUMEN
Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.
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Neoplasias de la Mama , Hormona Liberadora de Gonadotropina , Goserelina , Premenopausia , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/uso terapéutico , Goserelina/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , SupervivenciaRESUMEN
OBJECTIVES: Gonadotropin-releasing hormone (GnRH) test is the gold standard test to evaluate the hypothalamus-pituitary-gonadal (HPG) axis for the diagnosis of central precocious puberty (CPP). However, the diagnosis of cases with clinical features of CPP whilst have borderline peak luteinizing hormone (LH) remain challenges. We aimed to evaluate diagnostic performance of the average of LH levels measured during GnRH stimulation test. METHODS: Cases with diagnosis of CPP and premature thelarche (PT) who had a GnRH stimulation test results were retrospectively reviewed. Anthropometric measurements (weight, height, and body mass index), age and sex-specific standard deviation scores, growth velocity, puberty stages, bone ages, serum FSH, LH, and estradiol levels were measured by electrochemiluminescence immunological method (ECLIA), and the GnRH stimulation test results, which performed by obtaining venous blood samples at basal, 20th, and 40th minutes for FSH and LH measurement, were recorded. RESULTS: A total of 76 girls (38 CPP, 38 PT) were included. We detected an average peak LH cut-off value of 4.25â¯IU/L with 94.7â¯% sensitivity and 97.4â¯% specificity, a 97.3â¯% positive predictive value, and a 94.9â¯% negative predictive value in GnRH test to differentiate cases with CPP from PT. CONCLUSIONS: This is the first study evaluating the diagnostic utility of the average of LH levels measured during GnRH stimulation test. We showed that the average of two LH measurements has a high diagnostic performance. Therefore, it can be used as a valid and reliable diagnostic tool for assessment of HPG axis activation, particularly for cases with a borderline peak LH level.
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Hormona Liberadora de Gonadotropina , Hormona Luteinizante , Pubertad Precoz , Humanos , Hormona Luteinizante/sangre , Hormona Liberadora de Gonadotropina/sangre , Femenino , Pubertad Precoz/diagnóstico , Pubertad Precoz/sangre , Estudios Retrospectivos , Niño , Pronóstico , Estudios de Seguimiento , Biomarcadores/sangre , Hormona Folículo Estimulante/sangreRESUMEN
This study compared reproductive outcomes among two protocols for synchronization of ovulation that provide for a lengthened proestrus with the conventional oestradiol-based protocol currently used for timed-AI (TAI). Holstein heifers (13-15 months) at one location were assigned randomly to one of three TAI protocols. Heifers (n = 150) in the 7-day oestradiol benzoate (EB) group received a progesterone device (Cue-Mate) and 2 mg EB on Day 0; 500 µg of cloprostenol (PGF) and Cue-Mate removal on Day 7; 1 mg of EB on Day 8 and TAI on Day 9 (54 h after Cue-Mate removal). Heifers (n = 150) in the 5-day CO-Synch (CO) group received a Cue-Mate and 100 µg of gonadotropin-releasing hormone (GnRH) on Day 2; Cue-Mate removal and PGF (twice, 12 h apart) on Day 7; and GnRH along with TAI on Day 10 (72 h after Cue-Mate removal). Heifers (n = 150) in the J-Synch (JS) group received a Cue-Mate and 2 mg of EB on Day 1; PGF and Cue-Mate removal on Day 7; GnRH and TAI on Day 10 (72 h after Cue-Mate removal). Heifers were inseminated by one technician with frozen-thawed conventional semen from one of four commercially available sires. Plasma progesterone (P4) concentrations (ng/mL) were determined at Cue-Mate removal and TAI. Ovarian ultrasonography was done in a subset of 217 heifers at the initiation of protocols, at Cue-Mate removal; TAI; and 7 days after TAI. Approximately, 28 and 50 days after TAI pregnancy status was determined by ultrasonography. Mean (±SEM) plasma P4 concentration at Cue-Mate removal was greater (p < .01) in CO (6.02 ± 0.2) and JS (6.51 ± 0.2) compared to EB heifers (4.53 ± 0.2). Mean (±SEM) plasma P4 concentration at TAI was lowest in the JS (0.28 ± 0.05), intermediate in CO (0.46 ± 0.02), and greatest in EB heifers (0.66 ± 0.05, p < .01). The diameter of the ovulatory follicle (mean ± SEM) was the smallest in the JS group compared to that in the CO and EB groups (15.8 ± 0.5; 13.9 ± 0.5; and 12.7 ± 0.5 mm for EB, CO and JS, respectively). More (p < .01) heifers in the JS group had their oestrous cycle synchronized (50.0, 78.8 and 82.4% for EB, CO and JS groups), and were pregnant at 28 (40.3, 51.3 and 63.3% for EB, CO and JS groups) and 50 days after TAI (32.6, 46.0 and 60.0% for EB, CO and JS groups). In summary, heifers subjected to the J-Synch TAI protocol had lower P4 at TAI, and better overall response to hormonal treatments, which resulted in increased P/AI at 28 and 50 days after TAI compared to those heifers subjected to either a 7-day EB protocol or a 5-day CO-synch protocol.
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Cloprostenol , Estradiol , Sincronización del Estro , Hormona Liberadora de Gonadotropina , Inseminación Artificial , Progesterona , Animales , Bovinos/fisiología , Femenino , Sincronización del Estro/métodos , Inseminación Artificial/veterinaria , Inseminación Artificial/métodos , Progesterona/sangre , Progesterona/administración & dosificación , Progesterona/farmacología , Embarazo , Estradiol/administración & dosificación , Estradiol/farmacología , Estradiol/sangre , Estradiol/análogos & derivados , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/administración & dosificación , Cloprostenol/farmacología , Cloprostenol/administración & dosificación , Proestro , Índice de EmbarazoRESUMEN
PURPOSE: This study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing. METHODS: A retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes. RESULTS: Demographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4. CONCLUSION: For patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.
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Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Folículo Ovárico , Inducción de la Ovulación , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Estudios Retrospectivos , Adulto , Inyecciones de Esperma Intracitoplasmáticas/métodos , Embarazo , Fertilización In Vitro/métodos , Folículo Ovárico/efectos de los fármacos , Inducción de la Ovulación/métodos , Índice de Embarazo , Pronóstico , Antagonistas de Hormonas/uso terapéutico , Resultado del EmbarazoRESUMEN
OBJECTIVE: To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congenital hypogonadotropic hypogonadism (CHH). METHODS: We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023. We treated the patients with gonadorelin at 7ï¼15 µg, one pulse/90 min, and followed them up every month in the first 3 months and then every 3 to 6 months after treatment, for an average of 19.1±4.3 months, during which we recorded the height, body weight, penile length, testis volume, Tanner stages, levels of FSH, LH and T, semen parameters and adverse reactions of the patients, followed by comparison of the data obtained with the baseline. RESULTS: The levels of FSH, LH and T of the patients were dramatically elevated after treatment (P < 0.01). The T level of the 6 cases of cryptorchidism, however, failed to reach the normal value within 18.2 ± 8.6 months of follow-up. Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients, and spermatogenesis was observed in the semen in 33 cases (73.3%), with a mean sperm concentration of (18.2 ± 6.2) 106/ml, sperm progressive motility of (19.7 ± 6.5) %, and semen volume of (1.8 ± 0.6) ml. Eight of the cases achieved natural fertility, and another 3 achieved childbirth by assisted reproductive technology. As for adverse events, gynecomastia was observed in 8, subcutaneous induration in 6, and allergic reaction to therapeutic agent in 3 cases. CONCLUSION: Pulsatile GnRH therapy is an effective and safe strategy for male CHH. However, clinicians should choose appropriate approaches to different individual cases.