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1.
Oncol Res ; 32(8): 1309-1322, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055889

RESUMEN

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.


Asunto(s)
Preservación de la Fertilidad , Hormona Liberadora de Gonadotropina , Neoplasias , Ovario , Insuficiencia Ovárica Primaria , Humanos , Preservación de la Fertilidad/métodos , Femenino , Neoplasias/tratamiento farmacológico , Ovario/efectos de los fármacos , Ovario/metabolismo , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/prevención & control , Hormona Liberadora de Gonadotropina/agonistas , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Criopreservación/métodos
2.
J Assist Reprod Genet ; 41(8): 2185-2192, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38847932

RESUMEN

OBJECTIVE: Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. METHODS: A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. RESULTS: EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. CONCLUSION: Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.


Asunto(s)
Implantación del Embrión , Transferencia de Embrión , Endometrio , Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Resultado del Embarazo , Índice de Embarazo , Humanos , Femenino , Embarazo , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Adulto , Implantación del Embrión/efectos de los fármacos , Endometrio/efectos de los fármacos , Endometrio/patología , Hormona Liberadora de Gonadotropina/agonistas , Terapia por Acupuntura/métodos , Infertilidad Femenina/terapia , Infertilidad Femenina/tratamiento farmacológico
3.
Breast Cancer Res Treat ; 206(3): 543-550, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38709374

RESUMEN

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.


Asunto(s)
Inhibidores de la Aromatasa , Neoplasias de la Mama , Hormona Liberadora de Gonadotropina , Premenopausia , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Adulto , Estudios Retrospectivos , Hormona Liberadora de Gonadotropina/agonistas , Persona de Mediana Edad , Inhibidores de la Aromatasa/uso terapéutico , Ovario/efectos de los fármacos , Ovario/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Resultado del Tratamiento , Receptores de Estrógenos/metabolismo , Goserelina/uso terapéutico , Goserelina/administración & dosificación , Leuprolida/uso terapéutico , Leuprolida/administración & dosificación , Receptores de Progesterona/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
4.
Gynecol Oncol Rep ; 53: 101383, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38633671

RESUMEN

As more premenopausal patients undergo fertility preserving cancer treatments, there is an increased need for fertility counseling and ovarian sparing strategies. Many patients receive gonadotoxic chemotherapeutic agents which can put them at risk of primary ovarian insufficiency or profoundly diminished ovarian reserve. Traditionally, estradiol and follicle stimulating hormone (FSH) values have been used to evaluate ovarian function but more recently, reproductive endocrinologists have been proponents of anti-mullerian hormone (AMH) as a validated measure of ovarian potential. While the gold standard for fertility preservation remains oocyte cryopreservation, data suggest there may be additional interventions that can mitigate the gonadotoxic effects of chemotherapeutic agents. The main objectives of this focused review were to quantify the risk of primary ovarian failure associated with the most common chemotherapies used in treatment of gynecologic cancers and to evaluate and recommend potential interventions to mitigate toxic effects on ovarian function. Chemotherapeutic agents can cause direct loss of oocytes and primordial follicles as well as stromal and vascular atrophy and the extent is dependent upon mechanism of action and age of the patient. The risk of ovarian failure is the highest with alkylating agents (42.2 %), anthracyclines (<10-34 % in patients under 40 years versus 98 % in patients aged 40-49), taxanes (57.1 %) and platinum agents (50 %). Multiple trials demonstrate that gonadotropin releasing hormone (GnRH) agonists, when administered concurrently with chemotherapy, may have protective effects, with more patients experiencing resumption of a regular menstruation pattern and recovering ovarian function more quickly post-treatment. Premenopausal patients receiving chemotherapy for the treatment of gynecologic cancers should receive adequate counseling on the potential adverse effects on their fertility. Although oocyte cryopreservation remains the gold standard for fertility preservation, there is some evidence to suggest that GNRH agonists could help maintain and preserve ovarian function and should be considered.

5.
Horm Res Paediatr ; : 1-10, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684152

RESUMEN

INTRODUCTION: Phase 3 trial of 6-month subcutaneous leuprolide acetate (SC-LA) in children with central precocious puberty (CPP) demonstrated efficacy and safety. The aims of this secondary analysis were to evaluate unstimulated luteinizing hormone (LH) as efficacy measure, assess clinical suppression metrics, and present biochemical and clinical data for subgroups not achieving hormone suppression. METHODS: Sixty-two children with treatment-naïve CPP received 2 doses of 45 mg SC-LA at 24-week intervals. Unstimulated and GnRH-stimulated LH, E2, and T concentrations were measured. Clinical measures included bone age (BA) and predicted adult height (PAH). RESULTS: Eighty-four percentage and 86% of children achieved unstimulated LH <1 IU/L at weeks 24 and 48, respectively. Of 8 children not achieving unstimulated LH <1 IU/L at week 24 that completed the study, all showed a lack of pubertal stage progression and stable/decreased BA to chronological age ratio (BA/CA). Received operating characteristic (ROC) analyses suggested unstimulated LH is a good diagnostic predictor of GnRH-stimulated LH <4 IU/L at weeks 24 and 48 (AUC = 0.88). Across all children, mean BA/CA improved from 1.4 (screening) to 1.3 (week 48) and mean PAH increased by 3 cm. Of 7 girls not achieving stimulated LH <4 IU/L at week 24, all achieved E2 <10 pg/mL, showed a lack of pubertal stage progression, and had stable or decreased BA/CA by week 48. Additionally, 6/7 had increased PAH by week 48 and 4 had unstimulated LH <1 IU/L. CONCLUSION: Unstimulated LH has value as an efficacy measure and concentrations <1 IU/L may be an adequate surrogate of treatment response in children with CPP. All children who completed the study had evidence of pubertal suppression.

6.
Breast Care (Basel) ; 18(4): 270-278, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37900550

RESUMEN

Objectives: The aim of this study was to evaluate the effects of gonadotropin-releasing hormone agonists (GnRHas) on pregnancy outcomes, premature ovarian failure (POF), menstrual recovery, disease-free survival (DFS), and adverse events in premenopausal breast cancer patients during gonadal chemotherapy. Methods: We systematically searched PubMed, Cochrane Library, and Embase databases. The trials were eligible if they included premenopausal breast cancer patients treated with chemotherapy alone or with concurrent GnRHa and reported ovarian function recovery data. Heterogeneity for the eligible data was assessed, and a pooled risk ratio (RR) with 95% confidence interval (CI) was calculated. A meta-analysis was conducted using a fixed-effect model. Results: Fifteen randomized controlled trials were included in this analysis. The results indicated that GnRHa combined with chemotherapy significantly increased pregnancy rates compared with chemotherapy alone (RR = 1.76; 95% CI: 1.16-2.67) and decreased rates of POF (RR = 0.42; 95% CI: 0.35-0.51). For secondary endpoints, the GnRHa group improved menstrual recovery rates (RR = 1.20; 95% CI: 1.11-1.30) and decreased the rate of amenorrhea 1-2 years after chemotherapy (RR = 0.50; 95% CI: 0.40-0.63). Furthermore, the 5-year DFS and overall survival (OS) rates were significantly improved in the GnRHa group. Conclusion: For premenopausal breast cancer patients receiving gonadal toxic chemotherapy, adjuvant chemotherapy with GnRHa can better protect the ovarian function of patients, reduce the rate of POF and amenorrhea, and improve the pregnancy rate, menstrual recovery rate, DFS rate, and OS rate of patients.

7.
Annu Rev Med ; 74: 107-116, 2023 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-36260812

RESUMEN

Increasing numbers of transgender and gender-diverse (TGD) youth, from early puberty through late adolescence, are seeking medical services to bring their physical sex characteristics into alignment with their gender identity-their inner sense of self as male or female or elsewhere on the gender spectrum. Numerous studies, primarily of short- and medium-term duration (up to 6 years), demonstrate the clearly beneficial-even lifesaving-mental health impact of gender-affirming medical care in TGD youth. However, there are significant gaps in knowledge and challenges to such care. Long-term safety and efficacy studies are needed to optimize medical care for TGD youth.


Asunto(s)
Personas Transgénero , Humanos , Masculino , Femenino , Adolescente , Personas Transgénero/psicología , Identidad de Género , Salud Mental
8.
Ceska Gynekol ; 87(5): 356-361, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36316218

RESUMEN

Fertility preservation in cancer patients or oncofertility is a relatively new trend in modern medicine. In patients with unfulfilled reproductive plans, the possibility of starting a family is one of the key parameters of quality of life after overcoming a cancer. Guidelines have existed since 2013 and in 2020 the European Society of Human Reproduction and Embryology has also published a guideline, but the main problem of their application in clinical practice is the lack of information for both patients and, unfortunately, professionals, as well as the high cost of treatment. From 2022, health insurance companies in the Czech Republic partially cover the expenses for fertility preservation treatment for cancer patients. The possibilities of oncofertility are based, on the one hand, on improving the results of oncological treatment, on the other hand, on the development of reproductive technologies. Thanks to progress in treatment, up to 80% of pediatric oncology patients survive into adulthood, but chemotherapy, especially highly effective alkylating agents, is associated with a high risk of impaired fertility. This article overviewed9 modern global trends of fertility preservation in women undergoing cancer treatment based on an analysis of the English-language literature over the past 5 years.


Asunto(s)
Preservación de la Fertilidad , Neoplasias , Niño , Humanos , Femenino , Adulto , Preservación de la Fertilidad/métodos , Calidad de Vida , Criopreservación/métodos , Neoplasias/complicaciones , Neoplasias/terapia , Fertilidad , Oocitos
9.
Cureus ; 14(7): e26993, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35865181

RESUMEN

We present a novel case of severe hyperosmolar hyperglycemic derangement in an elderly patient - without a known history of diabetes mellitus - after the first injection of leuprolide for the treatment of metastatic prostate adenocarcinoma. Whilst the available literature provided accumulative evidence of an association between insulin resistance and the use of gonadotropin-releasing hormone (GnRH) agonists, the initial presentation of leuprolide-induced impaired glycemic tolerance with a hyperosmolar hyperglycemic state (HHS) represents a clinical rarity that was seldom reported. A literature review was conducted to explore the underlying mechanisms of leuprolide-associated glucose intolerance. Screening for diabetes is recommended for patients receiving leuprolide therapy to identify at-risk patients and close glycemic monitoring is warranted in diabetic patients to minimize serious complications from poor glycemic control induced by leuprolide.

10.
Front Endocrinol (Lausanne) ; 13: 826411, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35464066

RESUMEN

While triggering oocyte maturation with GnRH agonist (GnRHa) seems to be safe and effective in terms of the risk of developing OHSS and the number of metaphase II oocytes, it nevertheless results in luteal phase deficiency. To date, strategies have been developed in order to rescue defective luteal phase of GnRHa triggered cycles. Our study aimed to assess the reproductive outcome of GnRHa triggered cycles combined with modified luteal support (1500 IU hCG at the day of oocyte retrieval) in women with high ovarian response and to compare the outcome with hCG triggered cycles in GnRH antagonist IVF-ICSI procedures. A retrospective cohort database review of the results of GnRH antagonist IVF-ICSI cycles was conducted at a tertiary-care IVF center in Ljubljana, Slovenia. A total of 6126 cycles, performed from January 1, 2014, to December 31, 2020, were included in the final analysis. Final oocyte maturation was performed with either 5000, 6500, or 10,000 IU hCG (women with normal ovarian response) or 0.6 mg GnRHa (buserelin), supplemented with 1500 IU hCG on the day of oocyte retrieval (in women with high ovarian response). In cases of excessive ovarian response and/or high risk of OHSS luteal support was not introduced and all good quality blastocysts were frozen. According to significant differences in patients' age and the number of oocytes in the two groups, matching by age and number of oocytes was performed. No significant differences were observed regarding pregnancy rate per embryo transfer, rate of early pregnancy loss, and livebirth rate per pregnancy between the GnRHa and hCG trigger groups, respectively. A significant difference in the number of developed embryos and blastocysts, as well as the number of frozen blastocysts, was seen in favor of the GnRHa trigger. However, the birth weight in the GnRHa trigger group was significantly lower. Conclusion: The results of our study support the use of GnRHa for final oocyte maturation in GnRH antagonist IVF cycles in women with high ovarian response. Luteal phase rescue was performed by co-administration of 1500 IU hCG on the day of oocyte retrieval and estradiol and progesterone supplementation. In our experience, such an approach results in a comparable reproductive outcome with hCG trigger group.


Asunto(s)
Recuperación del Oocito , Síndrome de Hiperestimulación Ovárica , Gonadotropina Coriónica , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina , Antagonistas de Hormonas , Humanos , Recuperación del Oocito/métodos , Síndrome de Hiperestimulación Ovárica/prevención & control , Inducción de la Ovulación/métodos , Embarazo , Estudios Retrospectivos
11.
J Obstet Gynaecol ; 42(4): 665-669, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34396916

RESUMEN

The current study aimed to evaluate the clinical outcomes of patients with intravenous leiomyomatosis (IVL) who underwent myomectomy. Clinical data were retrieved from our database from January 2001 to October 2018. Of 197 patients with IVL, 9 (4.6%) patients were included. The patients' age ranged from 24 to 46 (mean: 31.1 ± 7.3) years. Five (55.6%) patients had not yet given birth upon IVL diagnosis. Three patients were treated with gonadotropin-releasing hormone agonists after surgery. The average follow-up time was 58.9 ± 27.8 (range: 29-122) months. Four patients presented with new uterine masses during follow-up. Three patients had natural pregnancies and live births. This information may provide a glimmer of hope to young patients with uterus-confined IVL who have fertility desires. However, future multicenter studies with larger sample sizes and longer follow-up periods are warranted.Impact statementWhat is already known on this subject? The best treatment options for intravenous leiomyomatosis (IVL) are hysterectomy with bilateral salpingo-oophorectomy and complete resection of intravenous extensions of the disease.What the results of this study add? Nine patients with IVL underwent myomectomy. After a mean follow-up period of 58.9 ± 27.8 months, 3 patients had natural pregnancies and live births.What are the implications of these findings for clinical practice and/or further research? The result might provide a glimmer of hope to young patients with uterus-confined IVL who have fertility desires.


Asunto(s)
Leiomiomatosis , Miomectomía Uterina , Neoplasias Uterinas , Enfermedades Vasculares , Adulto , Femenino , Humanos , Histerectomía , Leiomiomatosis/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Uterinas/cirugía , Adulto Joven
12.
BMC Cancer ; 21(1): 1259, 2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34809595

RESUMEN

BACKGROUND: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM. METHODS: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association. RESULTS: There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above. CONCLUSION: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH.


Asunto(s)
Diabetes Mellitus Tipo 2/inducido químicamente , Hormona Liberadora de Gonadotropina/agonistas , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Progresión de la Enfermedad , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Sistema de Registros , Análisis de Regresión , Suecia/epidemiología
13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1014936

RESUMEN

With an improvement in the long-term survival rates of cancer patients, the requirements for fertility protection of young cancer patients after chemotherapy are increasingly prominent. Early studies have shown that gonadotropin-releasing hormone agonist (GnRHa) has a protective effect on fertility. But in recenct year, relevant studies have shown that its protective effect is controversial. This article reviews the clinical researches of GnRHa for fertility protection in patients with common tumors, and explores its evidence-based medicine, in the hope of providing references for reasonable clinical application.

14.
J Endocr Soc ; 4(9): bvaa065, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32832823

RESUMEN

CONTEXT: Transgender youth may initiate GnRH agonists (GnRHa) to suppress puberty, a critical period for bone-mass accrual. Low bone mineral density (BMD) has been reported in late-pubertal transgender girls before gender-affirming therapy, but little is known about BMD in early-pubertal transgender youth. OBJECTIVE: To describe BMD in early-pubertal transgender youth. DESIGN: Cross-sectional analysis of the prospective, observational, longitudinal Trans Youth Care Study cohort. SETTING: Four multidisciplinary academic pediatric gender centers in the United States. PARTICIPANTS: Early-pubertal transgender youth initiating GnRHa. MAIN OUTCOME MEASURES: Areal and volumetric BMD Z-scores. RESULTS: Designated males at birth (DMAB) had below-average BMD Z-scores when compared with male reference standards, and designated females at birth (DFAB) had below-average BMD Z-scores when compared with female reference standards except at hip sites. At least 1 BMD Z-score was < -2 in 30% of DMAB and 13% of DFAB. Youth with low BMD scored lower on the Physical Activity Questionnaire for Older Children than youth with normal BMD, 2.32 ±â€…0.71 vs. 2.76 ±â€…0.61 (P = 0.01). There were no significant deficiencies in vitamin D, but dietary calcium intake was suboptimal in all youth. CONCLUSIONS: In early-pubertal transgender youth, BMD was lower than reference standards for sex designated at birth. This lower BMD may be explained, in part, by suboptimal calcium intake and decreased physical activity-potential targets for intervention. Our results suggest a potential need for assessment of BMD in prepubertal gender-diverse youth and continued monitoring of BMD throughout the pubertal period of gender-affirming therapy.

15.
J Clin Endocrinol Metab ; 105(10)2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738042

RESUMEN

CONTEXT: Gonadotropin-releasing hormone agonists (GnRHas) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by the Food and Drug Administration. OBJECTIVE: Determine efficacy, pharmacokinetics, and safety of 6-month 45-mg subcutaneous leuprolide acetate for CPP. DESIGN: Phase 3 multicenter, open-label, single-arm study. SETTING: 25 sites in 6 countries. SUBJECTS: 64 GnRHa-naïve children with CPP (age: 7.5 ± 0.1 years) received study drug: 59 completed the study. INTERVENTION(S): 2 doses of 45-mg subcutaneous leuprolide acetate (0.375 mL) at 0 and 24 weeks; children were followed for 48 weeks. MAIN OUTCOME MEASURE(S): Percentage of children with serum luteinizing hormone (LH) <4 IU/L 30 minutes following GnRHa stimulation at week 24. RESULTS: 54/62 (87%) children achieved poststimulation LH <4 IU/L at week 24; 49/56 (88%) girls and 1/2 boys maintained peak LH <4 IU/L at week 48. Mean growth velocity decreased from 8.9 cm/year at week 4 to 6.0 cm/year at week 48. Mean bone age was advanced 3.0 years beyond chronological age at screening and 2.7 years at week 48. Breast pubertal stage regressed or was stable in 97% of girls and external genitalia development regressed in both boys. Adverse events were mild and did not cause treatment discontinuation. CONCLUSIONS: A small volume of 45-mg subcutaneous leuprolide acetate administered at a 6-month interval effectively suppressed pubertal hormones and stopped or caused regression of pubertal progression. This long-acting GnRHa preparation of leuprolide acetate is a new, effective, and well-tolerated therapy for children with CPP.


Asunto(s)
Hormona Liberadora de Gonadotropina/agonistas , Leuprolida/administración & dosificación , Pubertad Precoz/tratamiento farmacológico , Niño , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/farmacocinética , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Subcutáneas , Leuprolida/efectos adversos , Leuprolida/farmacocinética , Masculino , Resultado del Tratamiento
16.
Expert Rev Clin Immunol ; 16(3): 321-333, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32005081

RESUMEN

Objectives: To systematically review risk of sustained amenorrhea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate efficacy of gonadotropin-releasing hormone agonists (GnRHa) to reduce this risk.Methods: Systematic search for papers reporting incidence of sustained amenorrhea ≥12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide compared to IV cyclophosphamide alone.Results: From 31 articles and 1388 patients (mean age 27.7 years) sustained amenorrhea occurred in 273 patients (19.7%). Of 56 patients (mean age range 23.9-25.6 years) receiving GnRHa and IV cyclophosphamide, and 37 controls (mean age range 25-30.1 years) given IV cyclophosphamide only, sustained amenorrhea occurred in 2/56 (3.6%) patients treated with GnRHa, compared to 15/37 (40.5%) controls. Pooled odds ratio of sustained amenorrhea with GnRHa and cyclophosphamide versus cyclophosphamide alone was 0.054 (95% CI 0.0115-0.2576 p < 0.001), corresponding to a number needed to treat of 2.7 (95% CI 1.955-4.388) and absolute risk reduction of 36.95% (95% CI 35.6-38.4%).Conclusion: Sustained amenorrhea with IV cyclophosphamide was observed in patients with ARD, especially with increasing age and cumulative doses >5 g. GnRHa reduced this risk and should be considered with IV cyclophosphamide in women of childbearing age with ARD.


Asunto(s)
Amenorrea/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/uso terapéutico , Enfermedades Reumáticas/tratamiento farmacológico , Administración Intravenosa , Adulto , Amenorrea/etiología , Ciclofosfamida/efectos adversos , Femenino , Humanos , Riesgo
17.
Front Neurol ; 11: 17, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32082242

RESUMEN

Purpose: The pubertal growth suppressive effects of gonadotropin hormone releasing hormone agonists (GnRHa) are well-known, although it remains unclear if long-term GnRHa treatment influences the brain function of treated children. The present study investigated the differences in the homotopic resting-state functional connectivity patterns in girls with idiopathic central precocious puberty (ICPP) with and without GnRHa treatment using voxel-mirrored homotopic connectivity (VMHC). Methods: Eighteen girls with ICPP who underwent 12 months of GnRHa treatment, 40 treatment-naïve girls with ICPP, and 19 age-matched girls with premature thelarche underwent resting-state functional magnetic resonance imaging using a 3T MRI. VMHC method was performed to explore the differences in the resting-state interhemispheric functional connectivity. The levels of serum pubertal hormones, including luteinizing hormone (LH), follicular-stimulating hormone, and estradiol, were assessed. Correlation analyses among the results of clinical laboratory examinations, neuropsychological scales, and VMHC values of different brain regions were performed with the data of the GnRHa treated group. Results: Significant decreases in VMHC of the lingual, calcarine, superior temporal, and middle frontal gyri were identified in the untreated group, compared with the control group. Medicated patients showed decreased VMHC in the superior temporal gyrus, when compared with the controls. Compared to the unmedicated group, the medicated group showed a significant increase in VMHC in the calcarine and middle occipital gyrus. Moreover, a positive correlation was observed between basal LH levels and VMHC of the middle occipital gyrus in medicated patients. Conclusions: These findings indicate that long-term treatment with GnRHa was associated with increased interhemispheric functional connectivity within several areas responsible for memory and visual process in patients with ICPP. Higher interhemispheric functional connectivity in the middle occipital gyrus was related to higher basal LH production in the girls who underwent treatment. The present study adds to the growing body of research associated with the effects of GnRHa on brain function.

18.
Arterioscler Thromb Vasc Biol ; 40(3): e55-e64, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31969015

RESUMEN

Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.


Asunto(s)
Antagonistas de Andrógenos/efectos adversos , Antineoplásicos Hormonales/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Sistema Cardiovascular/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Cardiotoxicidad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/terapia , Sistema Cardiovascular/fisiopatología , Humanos , Masculino , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
19.
Aging Male ; 23(5): 327-334, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29495911

RESUMEN

This study aimed to compare the skeletal effect between GnRH agonist therapy and orchidectomy in male rats assessed using serum turnover markers and bone histomorphometry. Three-month-old male Sprague-Dawley rats (n = 46) were divided into three experimental arms, baseline, buserelin, and orchidectomy. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline or buserelin acetate at 25 µg/kg or 75 µg/kg. In the orchidectomy arm, the rats were either sham-operated or orchidectomized. The rats were euthanized after the three-month treatment. Blood was collected for the evaluation of bone turnover markers. Femurs were harvested for bone histomorphometry examination. A significant increase in serum C-telopeptide of type 1 collagen was observed in the orchidectomized group compared with the sham group (p < .05). Structural histomorphometry analysis showed that both buserelin (25 µg/kg and 75 µg/kg) and orchidectomy significantly decreased the trabecular bone volume, number and significantly increased trabecular separation in rats compared with their respective controls (p < .05). Osteoclast number and eroded surface were significantly increased in both buserelin (25 µg/kg and 75 µg/kg) and orchidectomized group compared with their respective controls (p < .05). As a conclusion, buserelin causes deterioration of bone microarchitecture and increased bone resorption similar to orchidectomy after three months.


Asunto(s)
Buserelina , Orquiectomía , Animales , Remodelación Ósea , Huesos , Hormona Liberadora de Gonadotropina , Masculino , Ratas , Ratas Sprague-Dawley
20.
Cancer Manag Res ; 11: 4273-4282, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31190993

RESUMEN

Breast cancer remains the most common cancer among women worldwide. Many patients, especially in our region, are affected while young and during their child-bearing years. Chemotherapy, more commonly used in this age group, may result in premature ovarian failure and thus negatively impact their fertility. Several fertility-preservation methods are currently in use in this age group. Unfertilized ova cryopreservation and in vitro fertilization plus embryo cryopreservation are widely used in clinical practice. More recently, ovarian tissue cryopreservation is gaining in popularity. Several clinical trials and meta-analyses have shown that premenopausal women who received ovarian function suppression with gonadotropin-releasing hormone agonists while on chemotherapy were less likely to experience ovarian failure and had higher rates of menses resumption compared to those who did not. Some studies have also shown higher rates of successful pregnancies among treated patients. Given the conflicting results of the reported clinical trials and even the many published meta-analyses, this approach continues to be controversial and should only be used when other established fertility preservation methods cannot be utilized. The current review seeks to provide an updated summary on this controversial topic by reviewing all recently published clinical trials and meta-analyses.

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